Table 1.

Summarized data of EA protection against synthetic drugs’ adverse effects or toxicity

Toxic agent	Dose/Concentration period and route of exposure	Dose/Concentration of EA treatment period and route of administration	In vivo	Results	Reference
CPM	200 mg/kg, Single-dose, IP	10 mg/kg for 5 days, IP	Male Wistar rats	Decreased MDA, AOPP, and XO levels and increased the activities of GSH and CAT. Diminished ROS, AST, ALT, ALP, and GGT in the liver.	(18)
	15 mg kg, once a week, for 8 weeks, p.o	2 mg/kg every day, for 8 weeks, p.o	Male Sprague-Dawley rats	Ameliorated epididymal sperm concentration and motility, and decreased MDA level and oxidative stress. Increased Bcl-2 and reduced Bax in testicular tissue.	(19)
	15 mg kg, once a week, for 8 weeks, p.o	2 mg/kg, every day for 8 weeks, p.o	Male Sprague-Dawley rats	Improved the tail and total abnormality of sperm, plasma MDA level, erythrocyte SOD activity, and erythrocyte CAT activity in testicular tissue.	(20)
	50 mg/kg, single dose, IP	100 mg/kg, daily, for 7 days, p.o	Male Swiss albino mice	Decreased BUN, Cr, LDH MDA, and XO levels and increased GSH content, GPx, and CAT activities in the kidney.	(21)
	150 mg/kg, single dose, IP	15 mg/kg, daily, for 14 days, p.o	Male Wistar rats	Attenuated LPO, MPO, and NO production and protein carbonyl level. Increased GPx and reduced ROS generation in the lung.	(22)
CsA	15 mg/kg, daily, for 21 days, IP	10 mg/kg, daily, for 21 days, p.o	Male Sprague–Dawley rats	Ameliorated the weights of testes and ventral prostate, epididymal sperm concentration, motility, increased testicular tissue GSH and CAT, and decreased MDA levels.	(24)
	15 mg/kg, daily, for 21 days, s.c	10 mg/kg, daily, for 21 days, p.o	Male Sprague–Dawley rats	Significantly increased the GSH level, and CAT activities, and decreased MDA level of kidney, liver, and heart tissues.	(25)
	15 mg/kg, daily, for 30 days, p.o	10 mg/kg, daily, for 30 days, s.c	Male albino rats	Reduced oxidative stress, LPO, and MDA levels and elevated CAT and Px activities and testicular GSH concentration.	(26)
	25 mg/kg, daily, for 21 days, p.o	50 mg/kg, daily, for 21 days, p.o	Male albino Wistar rats	Decreased the activities of serum hepatic enzymes such as AST, ALT, ALP and LDH, and LPO.	(27)
Dox	5 mg/kg, twice a week, for 2 weeks, IP	10 mg/kg, daily, for 2 weeks, p.o	Male Sprague–Dawley rats	Improved testicular relative weight, sperm count, motility, serum testosterone, testicular glycogen. Decreased oxidative stress, and TNF-α.	(29)
	20 mg/kg, single dose, IP	1 g mixed with diet and given for 8 weeks, p.o	Male C57BL/6 mice	Reduced ROS, IL-6, IL-10 levels, MDA and XO activities, and monocyte chemoattractant protein-1 and TNF-α levels in the cardia.	(30)
	5 mg/kg, twice a week, for 2 weeks, IP	10 mg/kg, daily, for 14 days, p.o	Male Sprague–Dawley rats	Decreased MDA, TNF-𝛼, iNOS, caspase-3, and cholinesterase and increased GSH levels in the brain.	(31)
Gentamicin	100 mg/kg, single dose, IP	10 mg/kg, daily for 10 days, p.o	Male Sprague Dawley rats	Decreased LPO and MDA and increased CAT, SOD enzyme activity, and GSH content in kidney tissue. Increased the ratio of Bcl-2/Bax and prevented MMP loss in the kidney.	(33)
ISP	100 mg/kg, daily, for 2 days, s.c	15 mg/kg, daily, for 10 days, p.o	Male Wistar rats	Suppressed troponin-I, creatine kinase, LDH, C-reactive protein, and TBARS. Increased SOD, GST, and CAT and restored the GSH content in heart tissue.	(36)
MTX	20 mg/kg, single dose, IP	10 mg/kg, daily, for 10 days, p.o	Male Wistar rats	Decreased MDA levels, Bcl-2/Bax ratio, cytochrome-c release, and caspase-3/9 and decreased mitochondrial outer membrane potential. Up-regulation of both Nrf2 and HO-1in the liver.	(38)
	20 mg/kg, single dose, IP	10 mg/kg, daily, for 5 days, p.o	Male Wistar rats	Reduced MDA, NO, and PGE2 levels and diminished the activity of MPO and XO, and increased GSH content level in the intestinal tissue.	(39)
	20 mg/kg, single dose, IP	10 mg/kg, daily, for 10 days, p.o	Male Wistar rats	Reduced AST, ALT, ALP, MDA, and LPO. Increased SOD, CAT, and GST, and restored the GSH content level in the liver.	(40)
Paracetamol	500 mg/kg, single dose, p.o	100 mg/kg, daily, for 7 days, p.o	Swiss albino mice	Suppressed liver marker enzymes (ALT, AST, and ALP) in serum and MDA levels. Increased CAT and SOD activity and GSH level in the liver.	(42)
Sodium valproate	400 mg/kg, daily for 7 days, p.o	50 mg/kg, daily, for 10 days, p.o	Male Wistar rats	Protected the male rats' reproductive system against necrosis, atrophy in seminiferous tubules, multi-nucleated giant cell formation, and interstitial edema induced by sodium valproate.	(44)
STZ	3 mg/kg single dose, ICV	35 mg/kg, daily, for 4 weeks, p.o	Wistar rats	Decreased the TBARS and LDH content and depression of GSH levels and SOD and CAT activity in the brain of rats. Decreased AChE and LDH activity, TNF-α, and eNOS levels.	(46)
	50 mg/kg, single dose, IP	50 mg/kg, daily, for 21 days, p.o	Wistar albino rats	Reduced MDA, TOS, and NO levels Increased TAS level, CAT, and PON-1 activities in sciatic and brain tissue.	(47)

AChE: acetylcholinesterase; AOPP: advanced oxidized proteins products; ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; BUN: blood urea nitrogen; CAT: catalase; CPM: Cyclophosphamide; Cr: creatinine; CsA: Cyclosporine A; EA: ellagic acid; Dox: doxorubicin; eNOS: endothelial nitric oxide synthetase; GSH: Glutathione; GST: glutathione-S-transferase; GPx: glutathione peroxidase; GGT: gamma-glutamyl transferase; ICV: intracerebroventricular; IL-6 or 10: interleukin-6/-10; ISP: isoproterenol; IP: intraperitoneal; iNOS: inducible nitric oxide synthase; LPO: lipid peroxidation; LDH: lactate dehydrogenase; MTX: Methotrexate; MDA: malondialdehyde; MPO: myeloperoxidase; MMP: mitochondrial membrane potential; NO: nitric oxide; Nrf2: nuclear erythroid 2-related factor 2; Px: peroxidase; PGE2: prostaglandin-E2; PON-1: paraoxonase; p.o: oral; ROS: reactive oxygen species; STZ: streptozotocin; SOD: superoxide dismutase; TBARS: thiobarbituric acid reactive substances; TNF-α: tumor necrosis factor-alpha; TAS: total antioxidant status; TOS: total oxidant status; XO: xanthine oxidase