Evaluating the Acute Toxicity and In vivo Protective Effect of Standardized Andrographis paniculata Extract against Doxorubicin-induced Cardiotoxicity in Sprague-dawley Rats

Doxorubicin fights cancer effectively, but harms heart muscle. The current methods for managing doxorubicin's toxicity are limited. This study determined the acute toxicity and protective effect of a standardized Andrographis paniculata ethanolic leaf extract against doxorubicin-induced cardiotoxicity. The acute toxicity of the extract was first investigated before determining its protective effect. 24 Sprague-Dawley rats were allocated into four groups: normal, DOX, DOX+AP250, and DOX+AP125. Doxorubicin was administered intraperitoneally (4 mg/kg/week) for four weeks. Treatment groups received doxorubicin plus either 250 mg/kg or 125 mg/kg daily dose of Andrographis paniculata ethanolic extract for 4 weeks. The rats were subjected to echocardiography 24 hours prior to sacrifice. After sacrifice, blood and heart tissue were collected to analyze brain natriuretic peptide and troponin level by the enzyme-linked immunosorbent assay. Histopathology assessment of heart tissues was also performed using hematoxylin and eosin staining. Andrographolide content of the extract was determined by HPLC. The bulk capsule extract's lethal dose 50 (LD50) was determined to be above 4166 mg/kg BW and the andrographolide content was 8.98%. Andrographis paniculata extract (125 or 250 mg) mitigated doxorubicin-induced cardiotoxicity by decreasing serum brain natriuretic peptide and troponin level (p < 0.05), reversing histopathological alterations in heart tissue (p < 0.05), and improving fractional shortening, ejection fraction and heart rate. This study demonstrates that the standardized extract may be a non-toxic herbal and holds promise as a therapeutic agent for mitigating doxorubicin-induced damage in rats. Further studies are needed to elucidate its exact protective molecular mechanism of action.