The attenuation of doxorubicin-induced testicular toxicity with improved testicular histoarchitecture of mice by the bioactive compounds in leaves: Experimental and computational studies.

Doxorubicin, as an antibiotic causes toxicity in human tissues through the generation of oxidant species; however, (Solanaceae) is ethnopharmacologically and scientifically reported to possess antidotal activities. This study was designed to validate the antidotal potency of the plant's bioactive compounds on rats' testes following induction with doxorubicin through the evaluation of oxidative stress markers, lipid peroxidation indices, testes' histological sections, and profiling of the plant's bioactive compounds against some proteins. The collection and preparation of the plant extract, testicular toxicity induction, seminal analysis, assay of testosterone and oxidative stress markers, lipid peroxidation profiling, histomorphological studies, retrieval of catalase, superoxide dismutase, and glutathione peroxidase from PDB, GC-MS, ADME, and docking analyses followed standard protocols. In addition, Swiss-ADME and Auto Dock Vina 4.2 tool enabled drug-likeness, pharmacokinetic properties, and molecular docking analyses. The administration of differential dosages (70-210 mg/kg) of the extract to male rats induced with doxorubicin revealed that the serum levels of malondialdehyde (MDA), total cholesterol (TC), triglycerides (TG), LDL-C, and VLDL-C were significantly decreased, whereas significant increases were observed in the levels of HDL-C, testosterone, GSH, SOD, GPx, and CAT when compared to negative control animals. The histological findings suggested strong testicular protective potential that corroborated the chemical pathological alterations. Therefore, the compounds (squalene, β-sitosterol, cis-pinane, 1,4-Eicosadiene, 3,7,11,15-tetramethyl-2-hexadecen-1-ol, heptacosane, and bicyclo-heptanes-2,5,6-trimethylsilyl) characterized from leaf that revealed remarkable binding energies, pharmacokinetics, physicochemical, and drug-likeness properties contributed to the attenuation of the doxorubicin-induced testicular toxicity; hence, they possess antidotal activities.