The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice

Figures & data

Figure 1. A and B: H&E staining of liver tissues isolated from CCl₄-exposed rats demonstrates focal hepatocyte necrosis, as well as, increased infiltration of the inflammatory cells into the portal tract in the APAP-induced hepatotoxic mice; Fatty degeneration and central vein dilation were obvious (magnification ×400). C and D: No hepatocellular necrosis and APAP-induced damage was observed in metformin (200 mg/kg)- and NAC (100 mg/kg)-treated mice (magnification ×200).

Table 1. Histopathological evaluation of liver tissue obtained from control, APAP-induced hepatotoxic treated with either normal saline or metformin 200 mg/kg.

	Hepato-celluler Necrosis		Inflammatory Reaction		Apoptosis	Kuppfer cells	Fatty Changes		Vessels sinosoids
Group	zonal	Non zonal	Paran chymatous	Portal tracets	Nu/10	Hypertrophy	focal	diffuse	congestion	Regeneration
APAP (250 mg/kg/d)	–	+ + +	+ + +	++	17.23	+	–	+	+	–
Metformin (200 mg/kg/d)+ APAP (250 mg/kg/d)	–	−	+	+	6.23	–	–	–	–	–
NAC (100 mg/kg) + APAP(250 mg/kg/d)	–	−	−	+	5.17	–	–	–	–	–
Control	–	–	+	–	3.891	–	–	–	–	–

(+++) severe disorder; (++) moderate disorder; (+) weak disorder; (−) no effect.

Figure 2. The liver tissue levels of injury biomarkers (ALT, AST and ALP) in the control and subacute APAP-treated BALB/c mice receiving normal saline,metformin (50, 100 and 200 mg/kg) and NAC (100 mg/kg). The values are expressed as mean ± SD and analyzed using one-way ANOVA method followed by Tukey's post test. *p < 0.05, **p < 0.01, ***p < 0.001 compared to APAP/normal saline group; ⁺⁺⁺p < 0.001 compared to APAP/metformin 100 mg/kg group. ns: non-significant.

Figure 3. The liver tissue levels of MDA and antioxidants SOD and GSH activity levels in the control and subacute APAP-treated BALB/c mice receiving normal saline, metformin (50, 100 and 200 mg/kg) and NAC (100 mg/kg). The values are expressed as mean ± SD and analyzed using one-way ANOVA method followed by Tukey's post test. ***p < 0.001 compared to APAP/normal saline group; ⁺⁺⁺p < 0.05 compared to APAP/metformin 100 mg/kg group. ns: non-significant.

Figure 4. The serum levels of pro-inflammatory factors (IL-6, TNF-α and CRP) in the control and subacute APAP-treated BALB/c mice receiving normal saline, metformin (50, 100 and 200 mg/kg) and NAC (100 mg/kg). The values are expressed as mean ± SD and analyzed using one-way ANOVA method followed by Tukey's post test. *p < 0.05, ***p < 0.001 compared to APAP/normal saline group; ⁺p < 0.05 compared to APAP/metformin 100 mg/kg group; ⁺⁺⁺p < 0.001. ns: non-significant.