Carbon tetrachloride induced hepato/renal toxicity in experimental mice: antioxidant potential of Egyptian Salvia officinalis L essential oil

Abstract

The present research designed to assess the protective role of Salvia officinalis essential oil (SO) against carbon tetrachloride (CCl₄)-induced liver and kidney damage in mice. This is evidenced by estimation of antiradical scavenging activity of SO using DPPH assay, biochemical markers, histological investigation of liver and kidney sections, and comet assay. Mice were given CCl₄ (1.2 mL/kg for 24 h or 0.8 mL/kg for 2 weeks, 3 times/week) and with or without SO (0.1, 0.2, and 0.4 mL/kg, for 2 week, 5 times/week). The findings demonstrated that both acute and subacute treatment with CCl₄ alone had adverse side effects on liver and kidney of mice. These effects were evidenced by a significant increase in serum hepatic enzymes (ALT, AST, ALP, LDH, and G-GT), bilirubin, and renal function markers (blood urea, creatinine). Toxic effect of CCl₄ was accompanied by a decline in the serum total protein, albumin, globulin, and prothrombin (%). CCl₄ induced oxidative stress as evidenced by increasing serum lipid peroxidation (LPO) along with decreasing serum total glutathione S transferase (GST). A remarkable increase in hepatic DNA strand breakages and histopathological distortion in liver and kidney specimens were observed in CCl₄-intoxicated groups. Ultrastructurally, hepatocytes exhibited irregular nuclei, vacuolated cytoplasm, and distorted microorganelles. Essential oil form S. officinalis possessed antiradical scavenging (EC₅₀ = 4602 μg/mL) lower than ascorbic acid (EC₅₀ = 5.9 μg/mL). This oil was effectively exhibited hepato-nephroprotective activity especially at its higher concentrations in co-treated groups (SO plus CCl₄). The activity of SO was associated with lowering the liver enzymes, bilirubin, urea, and creatinine, along with increasing total protein, albumin, globulin, and prothrombin. The increase in GST content and the decrease in LPO and DNA breakage levels, alongside repairing the histo-architectural distortions further confirmed the protective activity of SO. SO is a potential candidate for counteracting hepato/renal injury associating CCl₄. This effect may occur via antioxidant defense mechanism which in part related to the complexity of its chemical constituents.

Keywords: Biochemical parameters; CCl4; Comet assay; DPPH; Hepato/renal protection; Histopathology; Salvia officinalis essential oil.