Protective Effects of 2‐(Thiophen‐2‐yl)‐2,3‐Dihydrobenzothiazole Against Rotenone‐Induced Multi‐Organ Toxicity in Sprague–Dawley Rats

Rotenone is a mitochondrial complex I inhibitor widely used to model neurotoxicity and systemic oxidative stress, and its damaging effects on peripheral organs remain a major safety concern. Benzothiazole derivatives possess antioxidant and cytoprotective properties and may mitigate xenobiotic-induced toxicity. This study investigated the protective effects of 2-(thiophen-2-yl)-2,3-dihydrobenzothiazole (ThBTH) against rotenone-induced multi-organ damage in male Sprague-Dawley rats. ThBTH was synthesized via condensation of 2-aminobenzenethiol with thiophene-2-aldehyde and administered at 10 mg/kg for 15 days (Days 1-15) before rotenone exposure (1.5 mg/kg) for the subsequent 15 days (Days 16-30). Blood samples and tissues of the kidney, liver, and heart were collected for serological and histopathological assessment. Rotenone significantly increased serum creatinine, urea, alanine aminotransferase, triglycerides, and cholesterol, whereas ThBTH pre-treatment markedly attenuated these alterations and restored values toward normal physiological ranges. Histopathological analysis revealed severe tissue degeneration and structural disruption in the kidneys, liver, and heart following rotenone administration, which were substantially reduced in ThBTH-treated animals. Overall, ThBTH conferred pronounced protection against rotenone-induced systemic toxicity, highlighting its potential as a promising cytoprotective candidate.