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Saudi Journal of Biological Sciences logoLink to Saudi Journal of Biological Sciences
. 2022 Nov 17;30(1):103507. doi: 10.1016/j.sjbs.2022.103507

Impact of Moringa oleifera leaf extract in reducing the effect of lead acetate toxicity in mice

Sahar J Melebary a,⁎, Moustafa HR Elnaggar b,c
PMCID: PMC9706165  PMID: 36458096

Graphical abstract

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Keywords: Blood chemistry, Histopathology, Lead acetate, Moringa oleifera, Mice, Toxicity

Abstract

This study aimed to assess the impact of Moringa oleifera (M. oleifera) leaf extract against the poisoning of lead acetate; therefore, sixty mice were allocated into 4 groups with 15 in each, as G1) blank control, G2) supplied with 300 mg/kg body weight (BWT). M. oleifera extract, G3) supplied with 60 mg/kg BWT of lead acetate [Pb(C2H3O2)2], and G4) supplied with extract of M. oleifera + lead acetate. The liver enzymes were elevated post-treatment with Pb(C2H3O2)2, which then lowered to almost the normal level when M. oleifera was supplied to mice previously treated with Pb(C2H3O2)2. The values in (G3) decreased when compared with G1 (92.33 ± 12.99, 21.67 ± 2.91 and 98.00 ± 13.20 U/L, respectively. Also, the cholesterol and low-density lipoprotein levels were elevated post-supplementation with M. oleifera and Pb(C2H3O2)2. Pb(C2H3O2)2 improves the lipid profile, whereas M. oleifera pretreatment reduced cholesterol (CHOL), high density low cholesterol (HDL-c), and low-density low cholesterol (LDL-c) levels in animals fed Pb(C2H3O2)2. Pb(C2H3O2)2 elevates the total protein but lowers the total bilirubin and triglycerides post M. oleifera treatment and Pb(C2H3O2)2 when contrasted with G1. The protective effect of M. oleifera was caused by the fact that it lowered triglycerides (TG) and total bilirubin (TBIL) and raised total protein (TP). After administration of Pb(C2H3O2)2, the histological examination revealed alterations in the hepatocytes and kidneys of G3. Also, the liver and kidney cells in mice supplied with M. oleifera after Pb(C2H3O2)2 poisoning recovered. In conclusion, Pb is toxic, and the usage of M. oleifera partially enhances the negative impacts induced by Pb(C2H3O2)2.

1. Introduction

Engineering, traffic, agriculture, and waste pollute the environment, resulting in toxic substances smogging the air, soil, food, and water, such as heavy metals (HMs), which endanger human health (Nagajyoti et al., 2010). HMs are considered the most poisonous ecological contaminants (Masindi and Muedi, 2018, El Zlitne, 2022).

Even at low levels, HMs have neurotoxic and oncogenic impacts on humans (Castro-González and Méndez-Armenta, 2008). Lead (Pb), mercury, cadmium, arsenic, and chromium are the most common heavy metals that can poison people, plants, animals, and fish. In addition, these HMs have various toxic impacts on different tissues (Balali-Mood et al., 2021). In 2016, Pb was deemed the cause of 540,000 deaths globally (Mu et al., 2019), and Pb contact is expected to be responsible for 0.6 % of the world's problem of diseases, especially in developing countries (WHO, 2011).

Pb is employed in many industrial processes, including the manufacture of ammunition, batteries, metal outcomes (solder and pipes), X-ray shielding devices, gasoline, paints, lead-based paint, toys, and cosmetics (Martin and Griswold, 2009, Nag and Cummins, 2022). Pb may be absorbed from the integument; it is mostly uptaken from the respiratory and alimentary tracts, leading to neurological, immunological, respiratory, renal, cardiovascular, skeletal, hematological, embryonic, and reproductive disorders because of disrupting the equilibrium of the oxidant-antioxidant agents and causing inflammation in different tissues (Guo et al., 2018, Zwolak et al., 2019, Usman et al., 2022).

The global blood level for Pb intoxication is 10 μg/dl (Kianoush et al., 2013). Wang et al. (2013) reported a marked elevation in the concentrations of AST, ALT, uric acid, creatinine, and serum urea in lead-exposed rats. Elmenoufy (2012) found that Pb treatment increased the creatinine, uric acid, bilirubin, and urea levels in exposed rats; moreover, Pb-exposed rats exhibited increased levels of total cholesterol, LDL, HDL, and TG, and also elevated ALP, GPT, and GOT enzymes. Pb(C2H3O2)2 altered hematological and biochemical profiles and revealed renal and hepatic damage via a significant increase in reactive oxygen species (ROS) formation, resulting in oxidative stress (OS), elevated lipid peroxidation, and a decrease in glutathione (GSH) levels in tissues (Ibrahim et al., 2011, Liu et al., 2012).

The histology and biochemistry of blood, kidney, liver and encephalon tissues were altered by Pb(C2H3O2)2 (Ozsoy et al., 2011). Recently, the world has been paying more attention to using natural products to improve the health of livestock (Alagawany et al., 2021, Abd El-Hack et al., 2022a, Abd El-Hack et al., 2022b, Arif et al., 2022). Chemical preparations can be dangerous (Alagawany et al., 2021, Abd El-Hack et al., 2022a, Abd El-Hack et al., 2022b, Arif et al., 2022) As a result, there is a high demand for the creation of antioxidant agents. Moringa species (spp.) are found in many tropical and subtropical parts of the world. Thirteen species of Moringa have been found (Lakshmidevamma et al., 2021).

Medicinal plants have many applications due to their efficiency, lower side effects, and content of phytochemical compounds that efficiently treat many diseases. Treatment of these diseases using efficient medicinal plants prevents or decreases infections. The global demand for natural goods has soared. Folk medicine, particularly herbal medications, is used to treat around 85 % of the population in underdeveloped nations. These requests are mostly motivated by the negative consequences of synthetic medications. As a result, the relevance of therapeutic herbs has grown dramatically. Identifying active herbal constituents can lead to new possible therapeutic uses and the manufacturing of natural pharmaceuticals, despite the long history of plant medicine use in traditional treatment systems. Great efforts should be made in the quality control of raw and manufactured pharmaceuticals to verify their use in the current healthcare system. Biological and clinical investigations are required to maximize the profitability of these plants. Furthermore, a practical plan for preserving medicinal plant resources should be devised. Medicinal herbs are used not only for adjuvant illness therapy but also for disease prevention and health maintenance.

M. oleifera Lam. is an abundant multipurpose plant of great importance. Almost every part of the tree is useful and has many industrial uses. This plant is considered a high-value crop due to its nutritive, curative, and preventative properties, which are linked to its high content of potent bioactive compounds (Lakshmidevamma et al., 2021, Brazales-Cevallos et al., 2022). M. oleifera has various therapeutic properties such as anti-cancer, anti-inflammatory, ulcer-healing, and antioxidant activities. The antioxidant and ROS-clearing properties of M. oleifera are attributed to its phenolic content (Paliwal et al., 2011, Chigurupati et al., 2022, Kandeepan et al., 2022).

Studies revealed the different dose-dependent impacts of extracts of M. oleifera on rats' renal tissues (Kasolo et al., 2012). Also, Nagashree et al. (2011) estimated the impact of M. oleifera on acute arsenic poisonousness in rats, and they found that the extract reduced the negative impact of arsenic. In addition, in rabbits, M. oleifera extracts reduced renal and hepatic histopathological changes caused by Pb(C2H3O2)2 (Mohamed et al., 2020). Therefore, this work was designed to determine the protective impact of M. oleifera leaf extract on blood chemistry. The tissue histopathology of mice subjected experimentally to lead acetate toxicity action revealed alterations in the hepatocytes and kidneys of G3. Also, the liver and kidney cells in mice supplied with M. oleifera after Pb(C2H3O2)2 poisoning recovered.

2. Materials and methods

2.1. M. oleifera leaves extraction

The leaves were carefully rinsed and dried at (20–25 °C), then powdered and preserved in a dry container according to Al-Attar and Abu Zeid (2013) with a few adjustments. After six hours, fifty grams of the powder were added to a flask containing 1.5 of hot water, and after six hours, the mix was gently boiled for 45 min. Post-treatment, the mix was cooled and then softly exposed to an electric mixer for 10 min. After that, the solution was filtrated with 250 mm filter paper, and then the filtrate was heat-treated at 40 °C to be evaporated and obtain dried active principles. The end product of the M. oleifera extracts was 16.4 % refrigerated for further work.

2.2. Laboratory animals

The mice were reared in cages and kept below normal lab circumstances such as humidity (65 %), temperature (20 ± 1 °C) and half in a half-light/dark cycle. Animals were fed ad libitum on a balanced ration with ad libitum clean water. Mice were adapted to the house for ten days prior to the beginning of the trial. The trial design and the animal handling procedures followed the ethical rules of the Animal Care and Use Committee of King Abdulaziz University.

As seen in Fig. 1, a total of 60 mice were allotted into 4 main groups (15 mice each) where.

  • 1.

    Control group (G1): mice supplied daily with distilled water via gastric intubations for 6 weeks,

  • 2.

    M. oleifera Leave extract supplied group (G2): animals were treated via oral route with 300 mg/kg BWT of M. oleifera leaves extract dose via the gastric intubation day post day for 6 weeks,

  • 3.

    Lead acetate-supplied group (G3): mice treated orally with 1/10 LD50 of Pb(C2H3O2)2 (60 mg/kg BWT) via the stomach tube, day post day for 45 days.

  • 4.

    M. oleifera Leave extract supplied group + lead (G4): mice orally administered 300 mg/kg BWT of M. oleifera leaves extract then given 60 mg/kg BWT Pb(C2H3O2)2 days after day for 45 days.

Fig. 1.

Fig. 1

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Experimental design and groups classification.

The BWT of mice was measured at the start of the trial and the end by a digital balance, and the health status was observed daily.

Blood was collected for biochemical assessment at the end of the trial (6 weeks). Animals in all groups were ethically slaughtered and examined, and sections of hepatic and renal tissues were taken for further histopathological examination.

2.2.1. Serum analysis

Mice abstained for 12 h with a constant water supply before being ethically sedated with diethyl ether. Blood was obtained from the orbital venous plexus in plain tubes and centrifuged at 2500 rpm for 15 min. The sera were separated and kept at 4 °C before direct evaluation of AST, ALT, ALP, Total bilirubin (TBIL), Lactate dehydrogenase (LDH), Total protein (TP), Glucose (GLU), Triglycerides (TG), Cholesterol (CHOL), High-density lipoprotein cholesterol (HDL-C), Low-density lipoprotein cholesterol (LDL-C), and Urea (BUN) (Abou-Kassem et al., 2021, Reda et al., 2021). Analysis was adopted via an automated clinical chemistry analyzer (RX DaytonaTM; Randox Laboratories, Crumlin, County Antrim, UK).

2.2.2. Histological examination

Mice were ethically dissected, and the livers and parts of the kidneys were kept in 10 % formal saline (Culling and Dunn, 1974, El-Saadony et al., 2021a). All liver and kidney specimens were processed and stained with H&E stain, then microscopically examined (Olympus BX61-USA) and snapped by a camera (Olympus DP72-USA) in the microscope unit at King Fahd Medical Research Center.

2.3. Heavy metals:

Samples of lead acetate and the rest of the chemicals were obtained from chemical companies in Jeddah.

2.3.1. Determination of LD50

The lethal and sub-lethal doses lethal dose (LD50) for is the concentration of Pb(C2H3O2)2 were determined in mice, and it was 600 mg/kg BWT.

2.4. Statistical analysis

The Statistical Package for Social Sciences (SPSS for Windows, version 12.0) was used to analyze the results. Values were articulated as means ± Standard Error, and values were tested by one-way analysis of variance (ANOVA). Afterward, the smallest significant difference (LSD) test was carried out to decide differences among the means of different groups, and p-values lower than 0.05 were significant.

3. Results

3.1. Biochemical findings:

3.1.1. The activity of ALT, AST, and ALP

As shown in Table 1, group 2 AST enzyme activities were significantly higher (p 0.05) when compared to G1 (187.4033.30 U/L) and increased for ALT and ALP when compared to G1 (36.251.84 and 75.2012.02U/L, respectively). The values in (G3) decreased when compared with G1 (92.33 ± 12.99, 21.67 ± 2.91 and 98.00 ± 13.20 U/L, respectively). When using M. oleifera leaves extract + Pb(C2H3O2)2 (G4), the mean values for the enzyme's activities were significantly lowered (p < 0.05) for AST and ALT when contrasted with G2 (97.00 ± 11.69 and 18.25 ± 3.17 U/L), but for ALP it was decreased (65.50 ± 15.06 U/L).

Table 1.

Mean values ± SE of the activities of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in different groups.

Parameters Groups AST (U/L) ALT (U/L) ALP (U/L)
Control 103.33 ± 6.13 24.00 ± 3.47 70.00 ± 2.12
M. oleifera 187.40 ± 33.30a 36.25 ± 1.84 75.20 ± 12.02
Lead acetate 92.33 ± 12.99 21.67 ± 2.91 98.00 ± 13.20
M. oleifera + Lead acetate 97.00 ± 11.69b 18.25 ± 3.17b 65.50 ± 15.06
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Values are given as means ± SE for 6 mice in each group.

a: Significantly increased when compared with control group (G1).

b: Significantly decreased when compared with M. oleifera group (G2).

3.1.2. Levels of HDL-C, CHOL and LDL-C

Table 2 illustrates the data when contrasting the mean values in M. oleifera leaves extract treated group (G2) with (G1) CHOL, and LDL-C were increased to 3.49 ± 0.29 and 0.29 ± 0.03 g/dl, respectively, while for HDL-C it was decreased to 2.91 ± 0.28 g/dl.

Table 2.

Mean values ± SE of cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) in different groups.

Parameters Groups CHOL (g/dl) HDL-C (g/dl) LDL-C (g/dl)
Control (G1) 3.32 ± 0.20 3.20 ± 0.06 0.23 ± 0.03
M. oleifera (G2) 3.49 ± 0.29 2.91 ± 0.28 0.29 ± 0.03
Lead acetate (G3) 3.98 ± 0.17 3.30 ± 0.003 0.64 ± 0.17a
M. oleifera + Lead acetate (G4) 3.33 ± 0.20 3.15 ± 0.09 0.41 ± 0.04
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Values are given as means ± SE for 6 mice in each group.

a: Significantly increased when compared with control group (G1).

b: Significantly decreased when compared with M. oleifera group (G2).

The values in (G3) were elevated for CHOL and HDL-C (3.98 ± 0.17 and 3.30 ± 0.003 g/dl, respectively) when compared with G1, but for LDL-C (0.64 ± 0.17 g/dl), it was significantly elevated (p < 0.05) when contrasted with G1.

When using M. oleifera + Pb(C2H3O2)2 in group (G4), the mean values decreased when compared with group 3 (3.33 ± 0.20, 3.15 ± 0.09 and 0.41 ± 0.04 g/dl, respectively).

3.1.3. The results of LDH, GLU and BUN

Table 3 shows the results of the lactate dehydrogenase enzyme activity (LDH), (GLU), and (BUN) in various groups examined. In (G1), the mean values ± SE for LDH, GLU, and BUN were 576.50 ± 13.25 U/L, 3.88 ± 0.80 and 8.44 ± 0.41 g/dl, respectively. When contrasting the mean values in the M. oleifera leave extract treated group (G2) with (GI), the enzyme LDH was increased (599.20 ± 0.80 U/L) while GLU and BUN were decreased (2.86 ± 0.20 and 8.26 ± 1.02 g/dl, respectively).

Table 3.

Mean values ± SE of lactate dehydrogenase (LDH) enzyme activity, glucose (GLU) and blood urea nitrogen (BUN) in different groups.

Parameters Groups LDH (U/L) GLU (g/dl) BUN (g/dl)
Control 576.50 ± 13.25 3.88 ± 0.80 8.44 ± 0.41
M. oleifera 599.20 ± 0.80 2.86 ± 0.20 8.26 ± 1.02
Lead acetate 577.00 ± 20.08 3.28 ± 1.029 12.30 ± 3.01
M. oleifera + Lead acetate 478.25 ± 73.49b, c 3.05 ± 0.39 7.03 ± 1.16d
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Values are given as means ± SE for 6 mice in each group.

b: Significantly decreased when compared with M. oleifera group (G2).

c: Significantly decreased when compared with control group (G1).

d: Significantly decreased when compared with lead acetate group (G3).

The mean values in (G3), when compared with (GI), were not changed for LDH enzyme (577.00 ± 20.08 U/L) and increased for BUN (12.30 ± 3.01 g/dl) and GLU (3.28 ± 1.029 g/dl). When using M. oleifera leaves extract + Pb(C2H3O2)2 (G4), the mean value of LDH was significantly decreased (478.25 ± 73.49 U/L) when compared with groups I and II, GLU was decreased (3.05 ± 0.39 mg/dl) when compared with GI and BUN was significantly decreased (7.03 ± 1.16 g/dl) when compared with group IV.

3.1.4. Levels of TP, TBIL and TG

Table 4 shows the results of TP, TBIL and TG in all groups. In G1, the mean values ± SE for TP, TBIL, and TG were 53.33 ± 1.52, 5.00 ± 0.26 and 0.92 ± 0.12 g/dl, respectively.

Table 4.

Mean values ± SE of total protein (TP), total bilirubin (TBIL) and triglycerides (TG) in different groups.

Parameters Groups TP (g/dl) TBIL (g/dl) TG (g/dl)
Control 53.33 ± 1.52 5.00 ± 0.26 0.92 ± 0.12
M. oleifera 59.00 ± 2.12a 4.80 ± 0.58 0.73 ± 0.08
Lead acetate 57.50 ± 2.53 4.75 ± 0.48 0.72 ± 0.22
M. oleifera + Lead acetate 52.00 ± 2.86 3.75 ± 0.25 0.83 ± 0.04
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Values are given as means ± SE for 6 mice in each group.

a: Significantly increased when compared with control group (G1).

When contrasting the mean values in the M. oleifera leave extract treated group (G2) with (GI), the TP was significantly increased (59.00 ± 2.12 mg/dl) while TBIL and TG were decreased (4.80 ± 0.58 and 0.73 ± 0.08 g/dl, respectively).

When comparing the mean values in (G3) with (GI), TP was increased (57.50 ± 2.53 g/dl), but TBIL and TG were decreased (4.75 ± 0.48 and 0.72 ± 0.22 g/dl, respectively).

When using M. oleifera leaf extract + Pb(C2H3O2)2 (G4), the mean values were decreased when compared with GIII for TP and TBIL (52.00 ± 2.86 and 3.75 ± 0.25 g/dl, respectively), but for TG it was increased (0.83 ± 0.04 g/dl).

3.2. Histological results

3.2.1. Liver

3.2.1.1. Light microscopy observations in (G1)

The liver tissues of G1 appear to be in normal shape. Fig. 2 shows the hepatic lobules, polygonal-appearing epithelial cells called hepatocytes, radiating from a central vein (CV). Hepatocytes make up each interconnected plate-like brick in a wall, and the plates are over the CV. The CV of every part is indicated by its location in the middle of each lobule, where portal areas are found at its periphery. Hepatocytes showed healthy and intact architecture with no necrosis of the liver cells. Blood sinusoids (liver sinusoids) lined with endothelial cells appeared as flattened cells with flattened nuclei. Specified cells, known as Kupffer cells (K) or satellite macrophages, are easily identifiable with H & E stain and found between sinusoidal endothelial cells (Fig. 2).

Fig. 2.

Fig. 2

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Histological section of A: liver in control group (G1) showing the hepatic lobules with its central vein (CV), notice the arrangement of hepatocytes as cords (H) separated by liver sinusoids (S), also appears Kupffer cells (K) also, a branch of the portal vein (PV) in the portal area (H & E stain  X  =  200); B: liver in control group (G1) showing branch of the portal vein (PV) and branch of the bile duct (BD) in the portal area, also hepatocytes (H) appeared normal with rounded nuclei (N) hepatocytes arranged in cords which are separated by liver sinusoids (S) also seen are Kupffer cells (K) (H & E stain X  =  400); C: liver in M. oleifera group (G2) showing normal arrangement of hepatocytes in cords (H) with rounded nuclei found in the middle of the cytoplasm (N) in addition, blood sinusoids appeared between hepatic cords (S), branch of the portal vein (PV) also, branch of the bile duct (BD) and Kupffer cells (K) are seen (H & E stain X  =  200); and D: liver in M. oleifera group (G2) showing normal arrangement of hepatocytes in cords (H) with rounded nuclei found in the middle of the cytoplasm (N) also, blood sinusoids appeared between hepatic cords (S), branch of the portal vein (PV), branch of the bile duct (BD) and Kupffer cells (K) are seen, and notice cytoplasmic vacuolation (V) (H & E stain X  = 400).

3.2.1.2. Light microscopy observations in (G2)

The liver section of (G2) appears to have a normal structure as (G1), where the hepatocytes appeared normal with rounded centrally located nuclei arranged in cords and blood sinusoids among the hepatic cords. Kupffer cells are clear with darkly stained nuclei (Fig. 2).

3.2.1.3. Light microscopy observations in (G3)

Histological liver testing in (G3) showed clear alterations in the hepatocytes represented by cytoplasmic vacuolation, granulation in some cells and pyknosis of the nuclei. In addition, some hepatocytes appeared to be undergoing necrosis and loss of their nuclei; in some sections, inflammatory cells appeared between hepatocytes, and there was congestion in blood vessels (Fig. 3).

Fig. 3.

Fig. 3

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Histological section of A: liver in lead acetate group (G3) showing congested branch of portal vein (PV), branch of bile duct (BD), granulation in cytoplasm of some cells (G), vacuolation of cytoplasm of some hepatocytes (V) and margination of nuclear envelope with chromatin (arrows) (H & E stain X  = 400); B: liver in lead acetate group (G3) showing inflammation cells (I), branch of portal vein congested with blood (PV), vacuolation of cytoplasm (dotted arrows) and granulation of cytoplasm (arrows), and also appeared Kupffer cells (K) (H & E stain X  = 400); C: liver in lead acetate group (G3) showing inflammation cells (I), branch of portal vein congested with blood (PV), vacuolation of hepatocytes’ cytoplasm (V) and pyknotic nuclei (double headed arrows) (H & E stain X  =  400); D: liver in lead acetate + Moringa oleifera group (G4) showing hepatocytes with normal cytoplasm (H), with rounded centrally located nuclei (N), some cells showing vacuolation in cytoplasm. Kupffer cells (K) and blood sinusoids (S) are seen clear (H & E stain X  = 400); E: liver in lead acetate + Moringa oleifera group (G4) showing normal hepatic cells (H) arranged in hepatic cords with normal rounded nuclei (N) centrally located in the cytoplasm, some cells showing vacuolated cytoplasm (V), central vein (CV) is clear also, Kupffer cells (K) and blood sinusoids (S) are seen clear (H & E stain X  = 400) and F: liver in lead acetate + Moringa oleifera group (G4) showing increasing in vacuolation in cytoplasm of hepatocytes (V) and hepatocytes (H) with faintly stained nuclei (N). also appeared, granules (G), the portal area with branch of hepatic artery (HA) and branch of bile duct (BD) also, appeared Kupffer cells (K) and blood sinusoids (S) (H & E stain X  = 400).

3.2.1.4. Light microscopy observations in (G4)

Examination of the liver in Pb(C2H3O2)2 + M. oleifera group (G4) revealed that the hepatic tissue appeared normal, resembling G1, where the hepatic cords were seen normal in arrangement and radiating around the central vein. The hepatic cells appeared normal with rounded nuclei and centrally located in the cytoplasm; some hepatic cells had vacuolated cytol and faintly stained nuclei, and blood sinusoids and Kupffer cells appeared normal (Fig. 3).

3.2.2. Kidney

3.2.2.1. Light microscopy observations in (G1)

The histological examinations of the kidney in (G1) revealed that the renal tissue could appear as a cortex and medulla. Each kidney contains millions of nephrons. A major part of each nephron is the corpuscles; a cortex dilated portion, proximal convoluted tubule and distal convoluted (Fig. 4) loop of Henle, which is thin and thick limbs, followed by the medulla back to the cortex. Collecting tubules (Fig. 4) from nephrons unite within collecting ducts to hold urine to the ureter. The renal capsule comprises a tuft of capillaries, the glomerulus, enclosed by a double-walled epithelial capsule, the Bowman's capsule, and the internal layer (the visceral layer) of the capsule envelops the capillaries of the glomerulus. The outer layer forms the limit of the renal capsules. Between the bilayers of Bowman's capsule is the urinary space. The parietal layer of Bowman's capsule, composed of simple squamous epithelium, rests on a basement membrane.

Fig. 4.

Fig. 4

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Histological section of A: kidney of mice of the control group (G1) showing the cortex with renal corpuscles (glomerulus) (G), inside the Bowman's capsule (BC) and the urinary space (US), proximal (PT), and distal (DT) convoluted tubules, which appeared normal with normal nuclei (N) (H & E stain X  = 600); B: kidney of mice of the control group (G1) showing the medulla with normal collecting tubules (CT), thin limb of Henle’s loop (T), thick limb of Henle’s loop (K) with normal healthy nuclei (N) (H & E stain X  = 400); C: kidney of mice treated with M. oleifera leaves extract (group G2) showing normal structures in cortex (C), medulla (M), glomerulus (G) and medullary rays (MR) (H & E stain X  = 200); and E: kidney of mice treated with M. oleifera leaves extract (group G2) showing normal collecting tubules (CT), thin (T) and thick (K) limbs of Henle’s loop (T) (H & E stain X  = 200).

3.2.2.2. Light microscopy observations in (G2)

Light microscopy observations of the kidney in the M. oleifera leaves extract treated group (G2) shows the normal kidney structure in both the cortex and medulla, where no changes in the glomerulus or the medullary rays (Fig. 4), While the structure of collecting tubules, thin and thick limb of Henle's loop also revealed normal structure (Fig. 4).

3.2.2.3. Light microscopy observations in (G3)

In (G3), the histological examination of kidneys of this group (Fig. 5) revealed significant alterations in proximal and distal convoluted tubules and collecting tubules (CT), thick Henle's loop (K) which characterized by vacuolation and necrosis of cells (Ne) with pyknotic nuclei also, the blood vessel (BV) among the tubules and the Henle loops were filled with blood with necrotic cells.

Fig. 5.

Fig. 5

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Histological section of A: kidney of mice of the lead acetate treated group (G3) showing collecting tubule (CT) with vacuolated cells and thick limb of Henle’s loop (K), many blood vessels filled with blood (thin arrows). Also seen many pyknotic nuclei and nuclear margination (arrow heads), and necrotic cells are also appeared (Ne) (H & E stain X  = 400); B: kidney of mice of the lead acetate treated group (G3) showing changes in distal convoluted tubules (DT) and proximal convoluted tubules (PT) also, seen collecting tubules (CT) which appeared lined by cells with vacuolated cytoplasm and disrupted shape. Also, found many pyknotic nuclei (arrow heads) (H & E stain X  = 400); C: kidney of mice of the lead acetate treated group (G3) showing blood vessels (artery and vein) (BV) and damaged glomerulus with distorted shape (DG) and many pyknotic nuclei (arrow heads), and nuclei with nuclear margination (thin arrow) (H & E stain X  = 400); D: kidney of mice of Moringa oleifera leaves extract and lead acetate treated group (G4), showing normal renal corpuscles with normal glomeruli (G) inside it and clear urinary space. Also, the parietal layer of Bowman’s capsule lined by squamous epithelium (arrow heads) (H & E stain X  = 600); E: kidney of mice of M. oleifera leaves extract and lead acetate treated group (G4), showing the cortex with regenerated collecting tubules (CT), thin (T) and thick (K) limbs of Henle’s loop (H & E stain X  = 400); and F: kidney of mice of Moringa oleifera leaves extract and lead acetate treated group (G4), showing Bowman’s capsule (BC) with glomerulus (G) inside it normal proximal convoluted tubule (PT), but distal convoluted tubule (DT) showed vacuolated cells, with pyknotic nuclei (thin arrow) (H & E stain X  = 600).

3.2.2.4. Light microscopy observations in (G4)

Mice in (G4) revealed normal structures of glomeruli, which appeared in the Bowman's capsules. The urinary space appeared clear, with the parietal layer of the Bowman's capsule appeared covered by squamous cells, and proximal and distal convoluted tubules also appeared normal in the cortex. However, in some sections, the distal convoluted tubules showed little changes, like cells with vacuolated cytoplasm and pyknotic nuclei. In the medulla, collecting tubules, thin and thick limbs of Henle's loop also showed normal structures (Fig. 5).

4. Discussion

Medicinal plants and natural secondary metabolites have recently grown in prominence in modern medical practice (Abd El-Hack et al., 2022c, Abd El-Hack et al., 2022d, El-Shall et al., 2022, El-Saadony et al., 2021b). Because herbal products are widely available, acceptable, inexpensive, and safe, there is trust in their use (Saad et al., 2021c, Saad et al., 2021b, Saad et al., 2021a, El-Saadony et al., 2020, El-Saadony et al., 2022a). As a result, the quality, efficacy, and safety of plant medicines have become major problems in both developed and developing countries. Moringa rich in antioxidants and other nutrients such as vitamins, minerals and amino acids, carotenoids, polyphenols, phenolic acids, flavonoids, alkaloids, glucosinolates, isothiocyanates, tannins and saponins (Swelum et al., 2021a, Swelum et al., 2021b, El-Saadony et al., 2022b). Therefore, the use natural components such as peptides (Abd El-Hack et al., 2021, Yaqoob et al., 2021), nano fertilizers (El-Saadony et al., 2021c, El-Saadony et al., 2021d, Elnahal et al., 2022), biofertilizers (Desoky et al, 2020b) in increasing Moringa trees growth and quality are crucial to worldwide trend in using the pure medicine.

Heavy metals toxicity is a serious global human health hazard (Usman et al., 2022, Desoky et al., 2020a). The data from this trial concluded that Pb(C2H3O2)2 induced toxicity and increases in the biochemical profile and histopathological alterations in renal and hepatic tissues. ALP, AST, and ALT levels were elevated post-supply with M. oleifera lead when contrasted with G1 (Table 1). These data concur with those of Sulliv)an (1996), who tested the impact of Pb toxicity on the serum AST, ALT, and ALP levels and reported that increased AST, ALT, and ALP levels result from Pb liver toxicity. Pb(C2H3O2)2-mediated hepatorenal toxicity and damage in male mice with significantly increased enzymatic activities of ALP, ALT, and AST (Götz et al., 1994, Farrag et al., 2007, Elmenoufy, 2012, Wang et al., 2013).

In this work, ALP, ALT, and AST activities were elevated post-treatment with lead and then lowered nearly to the normal level when supplied with M. oleifera to animals in (G4). These findings may be because of the protecting impact of M. oleifera. Kothandaraman and Dawood Sharief (2013) observed that administration of stannous chloride significantly increased AST, ALT, ALP, and ACP in blood serum compared with control. They added that the enzyme parameters significantly decreased in animals treated with M. oleifera, nearing the control values.

Therefore, they reported that supplementing with M. oleifera could minimize the toxic effects of stannous chloride. Also, Sharifudin et al. (2013) evaluated the impact of M. oleifera hydro-ethanol extract versus hepatic damage by hepatotoxin and acetaminophen, revealing an elevated level of (ALT & AST) in animals. They found that M. oleifera crude extracts decreased these enzymes' activities, thus lowering the seriousness of the liver injury. They suggested that M. oleifera leaf extract plays a critical role in treating the cause of acute hepatic damage in rats.

Similarly, Sharma et al. (2012) assessed the efficacy of M. oleifera as a liver protectant and antioxidant in comparison to 7,12-dimethylbenz[a] anthracene (DMBA), which caused liver cell destruction. They reported elevations in the activities of ALP, ALT, and AST, which indicate liver damage. Also, they added that pretreatment with M. oleifera markedly changed the DMBA, revealed changes in the hepatocytes, and offered almost complete protection. Their data indicated that M. oleifera shows a liver protective and antioxidant impact versus induced liver injury in mice.

In this study, the results of CHOL and LDL-c were elevated after treatment with M. oleifera and lead, while HDL-c was increased with M. oleifera and lead, when contrasted with (G1) (Table 2). Elmenoufy (2012) also found that adding lead to the diet raised the levels of CHOL and LDL-c by a large amount.

Pb(C2H3O2)2 alters biochemical and hematological profiles, revealing renal and hepatic toxicity via an increase in (ROS) formation and (OS), revealing an increase in lipid peroxidation and a decrease in GSH in renal and hepatic tissues (Ibrahim et al., 2011, Wang et al., 2011, Liu et al., 2012). Ozsoy et al., (2011) Pb always causes biochemical and histological changes in the blood, kidney, liver, and brain tissues. Ademuyiwa et al. (2005) recorded a positive relationship between blood lead and total cholesterol and LDL concentrations. Analyses of inflammation, in vitro investigations, and an investigation of occupationally subjected employees create a relationship between Pb and tumor necrosis factor-α (Valentino et al., 2007).

On the other hand, Ghasi et al. (2000) on M. oleifera supplied to a daily feed of laboratory rats, an increased level of cholesterol in the serum was recorded, which lowered drastically, and they concluded that M. oleifera leaves contain beta-sitosterol, which holds the capability to lower cholesterol level in blood. Also, M. oleifera in streptozotocin-diabetic Wistar rats only showed that it controls hyperglycemia (Tende et al., 2011).

In the present work, it was concluded that lead-induced increases in lipid profile, while pretreatment with M. oleifera for mice treated with lead, the concentrations of CHOL, HDL-c and LDL-c were lowered. These data prove the protective impact of M. oleifera against the toxicity of lead. In contrast with our data, Mazumder et al. (1999) recorded weekly therapy with M. oleifera significantly lowered cholesterol concentration.

In this work, it was found that supplementation of leaf extracts of M. oleifera lead caused increases in (LDH) enzyme and decreases in the values of (GLU) and (BUN) when contrasted with G1 (Table 3). These data are parallel with those of Farrag et al. (2007), who stated that lead intoxication revealed a marked elevation in blood urea and serum creatinine in rats given Pb. Also, Ashour et al.(2007) also studied the lead effect on serum glucose and renal action; they found that after oral supplementation of 1000 or 2000 ppm, Pb considerably lowered serum glucose.

The data of this work revealed that Pb induces increases in the values of (TP) but causes decreases in the values (of TBIL) and (TG) post-therapy with M. oleifera, lead, when contrasted with control (Table 4). In another study about lead toxicity made by Anetor et al.(2005), they found that total bilirubin, a degradative output of protoporphyrin, was markedly decreased in lead-exposed workers in comparison with controls, which agreed with the current findings. In this trial, administration of M. oleifera leaves causes decreases in total proteins, total bilirubin, and increases in triglycerides, which can be because of the protective impact of M. oleifera leaves extract.

The data of the histopathological investigation post supplementation of lead in this work revealed severe adverse hepatocyte alterations. Also, histological examination of the liver of Pb-exposed mice showed clear alterations in the hepatocytes. These findings agree with those of Jarrar and Taibb (2012), who investigated the histological and histochemical alterations due to Pb toxicity in the hepatic tissues of adult male Wistar rats. They found that exposure to Pb makes alterations in the liver.

In this work, the histological investigation of renal tissue of animals orally taken with Pb revealed severe alterations in renal tissues. These data concur with those of Farrag et al. (2007). They noticed that in rats supplied on the basal diet and eaten Pb, the renal corpuscle revealed congestion and hypercellularity, degeneration of the tubules, inflammatory infiltration, congested renal corpuscle and hemorrhagic parts in the interstitial region.

Also, the influence of lead exposure on the kidney of Wistar rats was evaluated by Missoun et al. (2010). They noticed an elevation of blood calcium, phosphaturia and calcium in rats supplied with lead contrasted with control ones, and the elevation of these showed a renal shortage that was inveterate by a lowering of creatinine and urea in urine samples and the existence of calcium oxalate dihydrate crystals in urine samples of exposed rats. All Pb-supplied animals in this trial revealed intranuclear inclusion bodies in the renal proximal tubular. The estimation of the level of Pb in the blood revealed that this agent elevated between supplied animals, also, they found that Pb supplied orally induces kidney defects in the rats.

In addition, Ghorbe et al. (2001) found that orally supplied with Pb revealed a considerable elevation in the blood urea and serum creatinine. In parallel, Pb intoxication reveals interstitial fibrosis and hyperplasia and gradual atrophy of tubules and glomeruli (Goyer, 1989, Nolan and Shaikh, 1992). Pb(C2H3O2)2 exposure revealed glomerular and tubulointerstitial alterations accompanied by glycosuria, proteinuria, kidney failure, and hypertension (Kim et al., 1996, Loghman-Adham, 1997). These findings support the current research results of lead intoxication of the kidney.

Additionally, Fakurazi et al. (2008) recorded the hepatoprotective impact of M. oleifera via the restoration of the hepatic enzymes in rats induced with acetaminophen. They also noticed that the pretreatment with this plant significantly saved rat hepatic histology. They recommended that the plant extract had action in maintaining basic cell integrity of the hepatocellular membrane, thus inhibiting enzyme leakage into the blood circulation. However, they also proposed that the caring impacts of M. oleifera leave versus chemical-caused liver toxicity were because of its ability to stimulate the phase II detoxification pathway through promoting GSH conjugation with toxic metabolites generated from CYP450 pathway (Fakurazi et al., 2008).

Azab (2014) investigated the liver protective effect of sesame oil versus Pb caused liver damage in albino mice from the histological and biochemical characteristics; they noticed that lead-supplied animals showed huge structural injury in the hepatocytes, and there were necrotic and degenerative alterations along with the presence of the inflammatory cell.

Sirimongkolvorakul et al. (2012) assessed the impact of M. oleifera on lowering the lead toxicity in Puntius Altus via histopathological examination in fishes, which were classified into three groups for supply with various M. oleifera levels; 0, 20, and 60 mg g-1 fish food, past month, they exposed fish to 93.8 mg/L (50 % of the 24 h LC50) of lead for 24 h. Then they noticed histopathologic changes in gills, kidneys, and livers, and they found changes in the structure of gills, kidneys, and hepatic tissues. However, M. oleifera-feeding fishes, particularly those with higher levels, noticed smaller scores in the histological changes when contrasted with the control fishes. Thus, these data indicate that pre-supplying M. oleifera would lower Pb(C2H3O2)2 damage in fish subjected to an ecosystem polluted with waterborne Pb(C2H3O2)2.

5. Conclusion

Pb(C2H3O2)2 is a toxic heavy metal that causes severe changes in blood biochemical parameters and histopathological changes in mouse hepatic and renal tissues. Moringa oleifera extract is rich in phytochemicals and exhibited various activities, therefore, using M. oleifera extracts partially enhances the negative impacts induced by lead. These results prove the protective impact of the M. oleifera extracts against lead toxicity. Further investigations were recommended to evaluate the impact of M. oleifera against different toxic materials while studying its applicability as a human herbal therapeutic agent.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Footnotes

Peer review under responsibility of King Saud University.

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