Abstract Xenobiotic-induced hepatotoxicity caused by environmental toxicants such as deltamethrin (DM) and carbon tetrachloride (CCl4) is largely mediated through oxidative stress and inflammatory injury to hepatocytes. Natural phytoconstituents including Diosgenin (DG) and Gallic Acid (GA) possess reported antioxidant and cytoprotective properties. The present study evaluated their hepatoprotective effects, administered individually and in combination, in experimental models of chemical-induced liver injury. A total of sixty-six Wistar albino rats (33 males and 33 females) were randomly allocated into eleven experimental groups (n = 6 per group). Animals were equally distributed by gender across groups (3 males and 3 females per group) to minimize gender-related variability; inclusion of both genders enhances translational applicability. Hepatotoxicity was induced using two established models: deltamethrin (10 mg/kg, orally, once daily for 28 consecutive days) or carbon tetrachloride (CCl₄; 1 ml/kg, 1:1 v/v in olive oil, orally, administered twice weekly for 28 days). Treatment groups received diosgenin (100 mg/kg), gallic acid (100 mg/kg), or their combination, while silymarin (50 mg/kg) was used as the standard hepatoprotective control. At the end of the treatment period, blood samples were collected for hematological analysis, including hemoglobin concentration, red blood cell count, white blood cell count, platelet count, and packed cell volume. Serum was further analyzed for biochemical markers of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, total protein and albumin. Liver tissues were harvested and subjected to histopathological examination to assess structural alterations. Exposure to DM and CCl4 produced significant hepatic injury characterized by elevation of serum ALT, AST, ALP, and bilirubin, reduction in protein markers, hematological alterations and marked histo-architectural damage. Treatment with DG or GA individually ameliorated these changes, while their combined administration produced greater normalization of biochemical, hematological and structural parameters. The protective response observed with the combination therapy was comparable to the standard drug silymarin. Diosgenin and Gallic Acid demonstrate significant hepatoprotective activity against chemically induced liver injury, with combined administration producing enhanced protective effects. The findings are supported by functional and histological recovery; however, mechanistic pathways were not directly investigated and warrant further molecular studies. Graphical Abstract (Experimental design: Rats were treated for 28 days. Hepatotoxicity was induced using either deltamethrin (daily oral administration) or CCl₄ (twice weekly oral administration). Diosgenin and gallic acid were administered orally 15 min prior to toxin exposure in respective groups. Combination groups received both compounds sequentially. Silymarin-treated groups served as standard controls). Highlights <UnorderedList Mark="Bullet"> <ItemContent> DM (pesticide) and CCL4induced significant hepatotoxicity in Wistar rats, evident from biochemical and histopathological alterations. </ItemContent> <ItemContent> DG and GA individually improved liver function and reduced hepatic damage. </ItemContent> <ItemContent> Combination therapy with DG and GA (1:1 ratio) showed enhanced hepa to protective effects. </ItemContent> <ItemContent> Treatment restored serum biochemical markers and hematological parameters (ALT, AST, ALP, bilirubin, total protein, albumin, RBC, WBC, Hb and platelets) toward normal. </ItemContent> <ItemContent> Histopathology confirmed attenuation of necrosis, inflammation and degeneration in treated groups. </ItemContent> <ItemContent> The protective efficacy of the DG-GA combination was comparable to the reference standard Silymarin. </ItemContent> <ItemContent> The study highlights the potential hepatoprotective effects of DG-GA combination, though the antioxidant and antiinflammatory mechanisms based on published literature but were not directly assessed in this work. </ItemContent> </UnorderedList>

Hepatoprotective effects of diosgenin and gallic acid against chemical-induced liver injury in rats

期刊论文
发表日期：

2026年6月30日

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Trilochan Satapathy,
Mansi Verma,
Poonam Sahu

摘要

Abstract

Xenobiotic-induced hepatotoxicity caused by environmental toxicants such as deltamethrin (DM) and carbon tetrachloride (CCl₄) is largely mediated through oxidative stress and inflammatory injury to hepatocytes. Natural phytoconstituents including Diosgenin (DG) and Gallic Acid (GA) possess reported antioxidant and cytoprotective properties. The present study evaluated their hepatoprotective effects, administered individually and in combination, in experimental models of chemical-induced liver injury. A total of sixty-six Wistar albino rats (33 males and 33 females) were randomly allocated into eleven experimental groups (n = 6 per group). Animals were equally distributed by gender across groups (3 males and 3 females per group) to minimize gender-related variability; inclusion of both genders enhances translational applicability. Hepatotoxicity was induced using two established models: deltamethrin (10 mg/kg, orally, once daily for 28 consecutive days) or carbon tetrachloride (CCl₄; 1 ml/kg, 1:1 v/v in olive oil, orally, administered twice weekly for 28 days). Treatment groups received diosgenin (100 mg/kg), gallic acid (100 mg/kg), or their combination, while silymarin (50 mg/kg) was used as the standard hepatoprotective control. At the end of the treatment period, blood samples were collected for hematological analysis, including hemoglobin concentration, red blood cell count, white blood cell count, platelet count, and packed cell volume. Serum was further analyzed for biochemical markers of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, total protein and albumin. Liver tissues were harvested and subjected to histopathological examination to assess structural alterations. Exposure to DM and CCl₄ produced significant hepatic injury characterized by elevation of serum ALT, AST, ALP, and bilirubin, reduction in protein markers, hematological alterations and marked histo-architectural damage. Treatment with DG or GA individually ameliorated these changes, while their combined administration produced greater normalization of biochemical, hematological and structural parameters. The protective response observed with the combination therapy was comparable to the standard drug silymarin. Diosgenin and Gallic Acid demonstrate significant hepatoprotective activity against chemically induced liver injury, with combined administration producing enhanced protective effects. The findings are supported by functional and histological recovery; however, mechanistic pathways were not directly investigated and warrant further molecular studies.

Graphical Abstract

(Experimental design: Rats were treated for 28 days. Hepatotoxicity was induced using either deltamethrin (daily oral administration) or CCl₄ (twice weekly oral administration). Diosgenin and gallic acid were administered orally 15 min prior to toxin exposure in respective groups. Combination groups received both compounds sequentially. Silymarin-treated groups served as standard controls).

Highlights

DM (pesticide) and CCL₄induced significant hepatotoxicity in Wistar rats, evident from biochemical and histopathological alterations.

DG and GA individually improved liver function and reduced hepatic damage.

Combination therapy with DG and GA (1:1 ratio) showed enhanced hepa to protective effects.

Treatment restored serum biochemical markers and hematological parameters (ALT, AST, ALP, bilirubin, total protein, albumin, RBC, WBC, Hb and platelets) toward normal.

Histopathology confirmed attenuation of necrosis, inflammation and degeneration in treated groups.

The protective efficacy of the DG-GA combination was comparable to the reference standard Silymarin.

The study highlights the potential hepatoprotective effects of DG-GA combination, though the antioxidant and antiinflammatory mechanisms based on published literature but were not directly assessed in this work.