Table 1.
Summarized results of the studies included in this review.
| Animal Model | Nephrotoxicity Model | Plant Preparation and Methods | Nephrotoxicity Evaluation | Main Results | Ref. |
|---|---|---|---|---|---|
| Adult male Wistar albino rats (8–9 weeks; 240–260 g) and female Swiss albino mice (8 weeks; 21–22 g) | IFO-induced renal injury (i.p. 50 mg/kg daily for 5 days) | TQ (5 mg/kg per day) for 5 days before and during IFO treatment. | Biochemical measurements: Creatinine, Creatinine Cl, Urea, Glucosuria, Phosphaturia, GSH, GST Enzymuria |
Significant amelioration of IFO-induced alteration in serum urea, creatinine, lipid peroxides and GSH in the TQ + IFO group (p < 0.05). | [62] |
| Adult male albino rats (160–180 g) | CP (i.p. 3 mg/kg for 5 alternate days) | NS extract (50 mg/kg body weight i.p.) before and after 30 min CP. | Mitochondrial oxidative phosphorylation Enzymes, Creatinine, Urea | NS reversed thetoxic effects caused by CP on Urea and creatinine serum levels. NS (given 30 min before cisplatin) partially prevented changes in the activities of serum enzymes. | [40] |
| Adult male albino rats (270–320 g) | CP (i.p. 3 mg/kg for 3 alternate days) | NS extract (100 mg/kg body weight, added in drinking water daily, after 2 weeks) | Serum creatinine, Urea, Triglyceride levels. Spot urine glucose. Histological evaluations. |
NS had non-significant effects on biochemical parameters. The histopathology properties of the kidneys relatively recovered after using NS. |
[41] |
| Adult male Wistar rats (180–245 g) | CP (i.p. 7 mg/kg in a single dose) | TQ (10 mg/kg in drinking water) for 5 days | Serum urea and creatinine; Lipid peroxidation (MDA and 8-isoprostane); OATs, OCTs and MRPs | Reduction of CP-induced MDA and 8-Isoprostane increments (p < 0.05) and significant increase in OATs and OCTs and up-regulation of MRPs in TQ + CP group | [42] |
| Adult male Wistar rats (150–200 g) | CP (i.p. 6 mg/kg in a single dose) | NSO (2 mL/kg orally) by gavage for 14 days prior to and 4 days following CP treatment. | Serum urea, creatinine and inorganic phosphate. Mitochondrial oxidative phosphorylation enzymes; product of LPO; RBBM and isolated RBBM vesicles. Histological evaluations. |
Pre-treatment with NSO is protective from CP-induced nephrotoxicity by enhancing the energy metabolism and restoring RBBM integrity. Histopathological observations showed reduced renal injury in CP + NS group. |
[44] |
| Adult male Wistar rats (200 g) | CP (i.p. 6 mg/kg in a single dose) + Particulate air pollution injury | TQ (20 mg/kg) orally by gavage from day 1 until 24 h before sacrifice. | Serum urea, creatinine. NAG, NGAL, IL-6, C-reactive protein, GSH, SOD, and catalase. Histological evaluations |
TQ significantly abrogated many of the effects of CP and diesel exhaust particle, given alone and in combination. | [47] |
| Adult male Wistar Albino rats (230–300 g) | CP (i.p. 6 mg/kg in a single dose) | NS (100 and 200 mg/kg) for 6 consecutive days. | Serum urea, creatinine. Urine osmolality. Oxidative stress indices (NO, LPO) |
Compared to vitamin, E.; NS significantly reduced the toxic effects of CP in a dose-dependent manner (p < 0.05). | [50] |
| Adult male Sprague-Dawley Rats (aged 26–28 weeks; weighed 250–350 g) | CP (i.p. 6 mg/kg; on the day, zeroth, 5th, 10th, 15th) | NS orally (400 mg/kg by tubing) and NS i.p. (50 mg/kg) | Serum urea, creatinine, (NAG, β-GAL), oxidative stress indices (NO, LPO), antioxidant activities (SOD), sulphur compounds (GGT, GSH), apoptotic indices (cathepsin, D.; DNA fragmentation) | M. Chamomilla + CP provided the best protection for the kidney followed by vitamin, E.; then NS orally and finally NS i.p. | [48] |
| Wistar Albino rats (8–9 weeks; 250–270 g). Swiss Albino mice (8 weeks; 18–20 g) |
CP (i.v. 5 mg/kg in rats; i.p. 7, and 14 mg/kg in mice) | TQ (4 mg/kg/day for rats and 8 mg/kg/day for mice) in drinking water for 5 days before and after cisplatin single injections | Serum urea and creatinine, Creatinine Clearance. Histological evaluations. |
TQ caused significant reductions in serum urea and creatinine and significant improvement in polyuria, kidney weight, and creatinine Clearance, as well as less tubular damage and loss. | [43] |
| Adult Swiss albino male mice (aged 4–6 weeks ; weighed 20–30 g) | MTX (i.p. 10 mg/kg weekly) | NSO (0.125 mL orally) for 21 days | MDA and GSH measurements on kidney homogenate. Histological evaluations | Unclear biochemical results. NS treatment resulted in preventing histopathological changes in all animals treated with NS + MTX. |
[53] |
| Male Sprague-Dawley rats | DOX (3.5 mg/kg i.p. twice weekly for 3 weeks) | TQ (50 mg/kg/day oral for 3 weeks) | Serum urea, creatinine, albuminuria, oxidative stress indices (SOD,GST), renal inflammation (TNF-α, IL-6,IL-10); NOX-4; Nrf2. Histological evaluations |
Treatment with TQ abrogated DOX-induced renal dysfunction (restored renal Nrf2 mRNA and Nrf2 binding activity) and tissue injury. | [56] |
| Male Wistar albino rats (180–200 g) | DOX (i.v. 6 mg/kg in a single dose) | TQ (10 mg/kg orally) 5 days prior DOX and until sacrifice | Serum urea, creatinine. Oxidative stress (LPO, non-protein sulfhydryl content, CAT). | Treatment with TQ substantially reduced both hyperlipidemia and hyperproteinuria; and restored the biomarker’s values of oxidative stress and nephrotoxicity towards normal. | [58] |
Legend. CP, cisplatin; CIN, chemotherapy-induced nephropathy; NS, Nigella sativa; IFO, ifosfamide; i.p., intraperitoneal; TQ, thymoquinone; GSH, glutathione; GST, glutathione S-transferase; MDA, malondialdehyde; OATs, organic anion transporters; OCTs, organic cation transporters; MRPs, multidrug resistance-associated proteins; CP, cisplatin; RBBM, renal brush border membrane; NO, nitric oxide; LPO, lipid peroxidation; NSO, NS oil; MTX, methotrexate; SOD, superoxide dismutase; NAG, N-acetyl-D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin; DOX, doxorubicin; TNF-a, tumor necrosis factor-a; IL-6, interleukin-6; IL-10, interleukin-10; NOX-4, NADPH oxidase 4; Nrf2, nuclear factor erythroid; i.v., intravenous; CAT, catalase. Nephrotoxicity evaluation may include biochemical measurements and histological evaluations.