TABLE 1.

Summary of the rutin‐induced protective effects on the liver

Toxic agent	Dose/concentration, period, and route of exposure (toxic agent)	Dose/concentration, period, and route of exposure (rutin)	Experimental model	Results of rutin exposure	Reference
Ethanol	0%–2% for 1 day	0–10 μM for 1 day	HepG2 cells and zebrafish	Decreased DRP1 and hepatic steatosis, and provoked remodeling of mitochondrial dynamics	(Choi et al., 2021)
	20% for 60 days	25, 50, and 100 mg/kg for 30 days	Male albino rats	Decreased AST, ALT, ALP, and GGT Increased SOD, CAT, GPx, and GST	(Shenbagam & Nalini, 2011)
	4%–7% for 24 h	5, 10, 20 μM for 1 h	HepG2 cells	Decreased ALT, AST, ROS, MDA, ROS, and NO Increased GSH and upregulated Nrf2	(Lee et al., 2019)
Carbon tetrachloride	2 ml/kg, 10% v/v, for 5 days (intraperitoneal)	10, 50, and 150 mg/kg for 5 days (intraperitoneal)	BALB/c mice	Decreased AST, ALT, NF‐κB, TNF‐α, COX‐2, and TGF‐β1 Increased SOD, GSH, Nrf2, and HO‐1	(Domitrović et al., 2012)
	3 ml/kg for 4 weeks (intraperitoneal)	70 mg/kg for 4 weeks (oral)	Male Wistar rats	Decreased AST, ALT, IL‐6, Bcl‐xl, MEK5, FADD, EGF, STAT3, and JAK Increased Bcl‐2	(Hafez et al., 2015)
	3 ml/kg for 4 weeks (intraperitoneal)	70 mg/kg for 4 weeks (oral)	Male Wistar rats	Decreased LDL, MDA, H2O2, AST, ALT, LDL, cholesterol, TGs, and MCP‐1 Increased CAT, GST, GPX, HDL, PON‐1, PON‐3, ABCA‐1, and PPARδ	(Hafez et al., 2014)
	3 ml/kg for 4 weeks (intraperitoneal)	50, 70 mg/kg for 4 weeks (oral)	Male Sprague–Dawley rat	Decreased ALT, AST, ALP, GGT, DNA fragmentation, and oxo8dG Increased SOD, CAT, GPx, GST, GR, GSH, p53, and CYP 2E1	(Khan et al., 2012a)
Mercuric chloride	1.23 mg/kg for 7 days	50 and 100 mg/kg for 1 week (oral)	Male Wistar rats	Decreased AST, ALP, ALT, and MDA Decreased EGFR, p53, p38 MAPK, Bax, procaspase‐3, cytochrome c, TNF‐α, IL‐1β, and NF‐κB Increased SOD, GPx, and GSH	(Caglayan, Kandemir, Darendelioğlu, et al., 2019)
5‐Fluorouracil	Single dose of 50 mg/kg	50 and 100 mg/kg, for 21 days (oral)	Male Sprague–Dawley rats	Decreased MDA, AST, ALT, LDH, ALP, and caspase‐3 Increased GPx, GSH, and Bcl‐2	(Gelen et al., 2017)
Thioacetamide	Single dose of 300 mg/kg (intraperitoneal)	10 mg/kg for 2 weeks (oral)	Male Wistar rats	Decreased AST, ALT, ALP, LDH, and DNA fragmentation	(Zargar et al., 2017)
Cadmium	150 mg/kg for 60 days (oral)	500 mg/kg for 60 days (oral)	Chicken	Decreased AST, ALT, MDA, ROS, NO, caspase‐8, iNOS, HSP27, HSP40, HSP60, HSP70, and HSP90 Increased CAT, SOD, GPx, JNK, ERK, P38, NF‐κB, TNF‐α, RIPK1, RIPK3, and MLKL	(Liu et al., 2022)
	Cd (50 mg/kg) + ethanol (5 mg/kg) for 15 days (oral)	25, 50, and 100 mg/kg for 2 weeks (oral)	Male Wistar rats	Decreased MDA, AST, ALT, ACP, GGT, cholesterol, and bilirubin Increased GSH, CAT, SOD, and GST	(Abarikwu et al., 2017)
Terutin‐butyl hydroperoxide	10 μM for 30 min and 2.5 mg/kg (intraperitoneal)	16.3 to 1.63 μM for 60 min 10, 50, and 100 mg/kg (oral)	Human erythrocyte and Swiss albino mice	Decreased ROS, MDA, TG, cholesterol, AST, ALT, ALP, bilirubin, and iNOS Increased GSH, CAT, GPx, GR, GST, SOD, and Nrf2	(Singh et al., 2019)
Methotrexate	Single dose of 20 mg/kg (intraperitoneal)	100 mg/kg (intraperitoneal)	Female Wistar rats	Decreased AST, ALT, and MDA Increased GSH and SOD	(Erdogan et al., 2015)
Cyclophosphamide	Single dose of 150 mg/kg (intraperitoneal)	50 and 100 mg/kg for 20 days (oral)	Male Wistar rats	Decreased AST, ALT, LDH TNF‐α, IL‐6, p38 MAPK, NF‐κB, iNOS, and COX‐2 Increased GSH, GPx, GR, CAT, XO, and LPO	(Nafees et al., 2015)
Deltamethrin	1.28 mg/kg (oral)	25 and 50 mg/kg for 30 days	Male Wistar rats	Decreased ALT, AST, ALP, TNF‐α, NF‐κB, IL‐1β, p38 MAPK, COX‐2, iNOS, beclin‐1, Bax, caspase‐3, PARP‐1, VEGF, and c‐fos Increased SOD, CAT, GPx, GSH, and Bcl‐2	(Küçükler et al., 2021)
Oxytetracycline	100 mg/kg for 2 weeks (oral)	1.5 g/kg for 2 weeks (oral)	Silver catfish	Decreased ALT, AST, MDA, HSP70, HMGB1, and caspase‐3 Increased SOD, CAT, GSH, GPx, GR, and G6PDH	(Londero et al., 2021)