Abstract
Mercury chloride (HgCl₂) is a widespread environmental contaminant that can induce multi-organ toxicity. This study evaluated the dose-dependent effects of subacute oral HgCl₂ exposure on hepatic and renal function in rats. It examined the relationship between oxidative stress, proinflammatory cytokine release, and the histological transition from reversible injury to irreversible necrosis. Thirty-two adult male Wistar rats were randomly allocated to four groups (n = 8/group): control (distilled water) and HgCl₂ at 1, 2, or 4 mg/kg body weight, administered daily by oral gavage for 28 days. Hepatic and renal function (ALT, AST, creatinine, blood urea nitrogen), oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]), and proinflammatory cytokines (TNF-α, IL-6) were measured, and liver and kidney sections were evaluated histologically. Data were analyzed by one-way ANOVA with Tukey's post-hoc test (α = 0.05). HgCl₂ produced a significant, dose-dependent impairment of hepatic and renal function. At the highest dose (4 mg/kg), serum ALT (220.6 ± 12.3 U/L) and AST (245.7 ± 15.8 U/L) were markedly elevated relative to controls (p < 0.001), together with creatinine and BUN. Lipid peroxidation peaked at 10.5 ± 0.9 nmol/mg protein, accompanied by a 73% reduction in SOD activity. In comparison, TNF-α (68.9 ± 4.3 pg/mg protein) and IL-6 (54.1 ± 3.8 pg/mg protein) rose significantly, consistently with activation of an inflammatory signaling cascade. Histopathology revealed a dose-dependent progression from reversible vascular congestion and fatty change at lower doses to irreversible hepatic and renal necrosis at 4 mg/kg only. To our knowledge, few prior subacute studies have concurrently characterized biochemical, inflammatory, and histological indices of hepatorenal injury within a single dose-response exposure protocol in the same animals, and effect sizes (partial η²p) and 95% confidence intervals were calculated for all pairwise comparisons. These findings indicate that HgCl₂-induced hepatorenal injury is associated with concurrent, potentially interacting effects of oxidative stress and inflammatory signaling. Because these processes were measured concurrently rather than experimentally manipulated, a causal mechanistic relationship cannot be established by the present design. The findings nonetheless support the combined use of biochemical, oxidative, and inflammatory biomarkers for early detection of mercury-induced organ injury.

Key words: Mercuric Chloride; Reactive Oxygen Species; Inflammation; Biomarkers; Oxidative Stress; Nephrotoxicity; Hepatotoxicity; Heavy Metals; Rats.