Cosmos Caudatus Extract Attenuates Doxorubicin-Induced Renal Histopathological Injury in Female Wistar Rats

Abstract

Doxorubicin remains a backbone of chemotherapy, yet its clinical utility is increasingly constrained by off-target organ injury, including nephrotoxicity. Here, we investigated whether an ethanolic extract of Cosmos caudatus, an edible medicinal herb widely consumed in Southeast Asia, can attenuate doxorubicin-induced renal histopathological damage in a preventive in vivo model. Female Wistar rats (6-8 weeks; 220-280 g) were allocated to three groups (n = 5/group): normal control (NC; vehicle), doxorubicin (DOX; 5 mg/kg intraperitoneally once weekly for 4 weeks; cumulative dose 20 mg/kg), and doxorubicin plus C. caudatus extract (DOX+CCE; 200 mg/kg/day by oral gavage with 1-week pretreatment and continued daily dosing during the 4-week doxorubicin regimen). At study completion, left kidneys were collected, H&E-stained, and evaluated by a blinded pathologist using the compartment-resolved EGTI scoring system (endothelial, glomerular, tubular, and interstitial domains); group differences were analyzed by two-way ANOVA followed by Tukey’s multiple-comparisons test. Histological examination showed preserved cortical architecture in NC, while DOX exposure produced diffuse tubular epithelial injury with prominent tubulointerstitial involvement. Consistent with these qualitative findings, DOX significantly increased injury scores across all EGTI domains versus NC (all p < 0.0001). Co-treatment with C. caudatus significantly reduced lesion severity in each domain compared with DOX alone (endothelium p = 0.0071; glomerulus p = 0.0240; tubules p = 0.0018; interstitial p = 0.0004) and lowered the total EGTI score (p < 0.0001), although scores remained above NC, indicating partial protection under the present regimen.