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Protective Effects of 2-(Thiophen-2-yl)-2,3-Dihydrobenzothiazole Against Rotenone-Induced Multi-Organ Toxicity in
Sumaira Kanwal1, Shazia Perveen2, Imran Haider3,4
1Department of Biosciences, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan.
Abstract:
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.
Insights
This study shows that 2-(thiophen-2-yl)-2,3-dihydrobenzothiazole (ThBTH) protects against rotenone-induced organ damage. ThBTH pre-treatment significantly reduced toxicity markers and preserved tissue integrity in rats exposed to rotenone.
Area of Science:
- Toxicology
- Pharmacology
- Biochemistry
Background:
- Rotenone, a mitochondrial complex I inhibitor, induces neurotoxicity and systemic oxidative stress.
- Peripheral organ damage from rotenone is a significant safety concern.
- Benzothiazole derivatives exhibit antioxidant and cytoprotective effects.
Purpose of the Study:
- To investigate the protective effects of 2-(thiophen-2-yl)-2,3-dihydrobenzothiazole (ThBTH) against rotenone-induced multi-organ damage.
- To evaluate ThBTH's efficacy in mitigating rotenone's systemic toxicity in male Sprague-Dawley rats.
Main Methods:
- ThBTH was synthesized and administered to rats for 15 days prior to rotenone exposure.
- Blood samples and kidney, liver, and heart tissues were collected for serological and histopathological analysis.
- Biochemical markers (creatinine, urea, ALT, triglycerides, cholesterol) and tissue integrity were assessed.
Main Results:
- Rotenone significantly elevated serum creatinine, urea, ALT, triglycerides, and cholesterol.
- ThBTH pre-treatment markedly attenuated these biochemical alterations, restoring values toward normal ranges.
- Histopathological analysis showed reduced tissue degeneration and structural disruption in ThBTH-treated animals compared to rotenone-only treated animals.
Conclusions:
- ThBTH demonstrated significant protective effects against rotenone-induced systemic toxicity.
- ThBTH attenuated biochemical and histopathological damage in the kidney, liver, and heart.
- ThBTH shows potential as a cytoprotective agent against xenobiotic-induced organ damage.
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