Dose-Dependent Hepatotoxicity in Wistar Rat Neonates From Early-Life Arsenic Exposure

Arsenic, a highly toxic heavy metal widely found in the environment, is a known carcinogen and toxin. Our study examined the effects of sodium arsenite on Wistar rat neonates exposed during gestation and weaning periods. The pregnant and weaning rats were given the low dose (LDG), median dose (MDG), and high dose (HDG) daily as 8.2, 12.3, and 16.4 mg/kgbw of NaAsO₂, respectively. The results revealed that despite not affecting litter size, gestation index, or immediate postnatal observations, prolonged exposure to high doses of sodium arsenite led to increased liver weights, indicating potential liver stress or damage. Arsenic accumulation in liver tissues was significant, and histological examinations revealed liver damage, vascular congestion, and inflammation. Elevated levels of ALT, AST, ALP, and GGT were observed in arsenic-exposed groups during liver function tests, indicating hepatocellular injury and impaired function. Exposure to arsenic led to a dose-dependent decline in the mRNA expression levels and activity of antioxidant enzymes, including GST, GR, GPx, SOD, and CAT, showing that oxidative stress is present. Furthermore, LPx levels were increased. Metallothionein gene expression was upregulated, indicating a protective response against arsenic toxicity. Our findings underscore the risks associated with gestational and weaning exposure to sodium arsenite, providing insight into potential mechanisms behind arsenic-induced health issues and highlighting the importance of understanding these risks during critical developmental stages.