Effect of arsenic acid withdrawal on hepatotoxicity and disruption of erythrocyte antioxidant defense system

- Arsenic acid increased both hepatic and erythrocyte enzymic and non-enzymic antioxidant defense system following exposure.
- Arsenic acid induced hepatotoxicity via free radical generation and oxidative stress.
- Hepatic antioxidant defense system partially recovered after withdrawal of the exposed arsenic acid.
- Arsenic acid toxicity enhanced protein kinase B (Akt/PKB) signaling pathway.

We investigated the effects of withdrawal from Sodium arsenite (NaAsO2) on the hepatic and antioxidant defense system in male Wistar rats using a before and after toxicant design. Rats were orally gavaged daily with varying doses of NaAsO2 for a period of 4 weeks. One half of the population was sacrificed and the remaining half had the toxicant withdrawn for another further 4 weeks. Biochemical and immunohistochemical techniques were used to assess the impact of withdrawal on the erythrocyte and hepatic systems. Exposure of Wistar rats to NaASO2 led to a significant (p < 0.05) increase in hepatic and erythrocyte markers of oxidative stress (malondialdehyde, thiol contents and hydrogen peroxide generation). Concurrently, there was a significant (p < 0.05) increase in hepatic and erythrocyte antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and superoxide dismutase) following exposure. Withdrawal from NaAsO2 exposure led to a decline in both erythrocyte and hepatic markers of oxidative stress and together with a significant improvement in antioxidant defense system. Histopathology and immunohistochemistry revealed varying degrees of recovery in hepatocyte ultrastructure alongside increased expression of the pro-survival protein Kinase B (Akt/PKB) after 4 weeks of NaAsO2 withdrawal. Conclusively, withdrawal from exposure led to a partial recovery from oxidative stress-mediated hepatotoxicity and derangements in erythrocyte antioxidant system through Akt/PKB pathway.

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