Luteolin abates reproductive toxicity mediated by the oxido-inflammatory response in Doxorubicin-treated rats

Abstract

The anti-neoplastic use of Doxorubicin (DOX) is hampered by several limitations, including reproductive toxicity. Luteolin (LUT)–a phytochemical-biological benefits include antioxidative and anti-inflammatory actions. Here we examined the protective effect of LUT against DOX-induced reproductive toxicity in an in vivo model—male albino Wistar rats—randomly assigned to five groups and treated as follows: Control (corn oil 2 mL/kg; per os), LUT (100 mg/kg; per os), DOX (2 mg/kg) by intraperitoneal injections, co-treated groups received LUT (50 and 100 mg/kg) with DOX. Treatment with DOX alone, significantly (p > 0.05), reduced biomarkers of testicular function, reproductive hormone levels, testicular and epididymal antioxidant, and anti-inflammatory cytokine. DOX increased (p > 0.05) sperm morphological abnormalities, as well as reactive oxygen and nitrogen species, lipid peroxidation, xanthine oxidase, a pro-inflammatory cytokine, and apoptotic biomarkers. Furthermore, testicular and epididymal histological lesion complemented the observed biochemical changes in treated rats. LUT co-treatment resulted in a dosage-dependent improvement in rats’ survivability, antioxidants capacity, reduction in biomarkers of oxidative stress, pro-inflammatory cytokines, and apoptosis in rat’s testis and epididymis. Also, LUT treatment resulted in improved histological features in the testis and epididymis, relative to DOX alone treated rats. LUT co-treatment abated DOX-mediated reproductive organ injuries associated with pro-oxidative, inflammatory, and apoptotic mechanisms. LUT supplementation may serve as a phyto-protective agent in alleviating male reproductive organ toxic injuries associated with Doxorubicin therapy.

Caffeic acid mitigates aflatoxinB1‐mediated toxicity in the male rat reproductive system by modulating inflammatory and apoptotic responses, testicular function, and the redox‐regulatory systems

“…A significant perturbation in the dynamic processes of spermatogenesis is evidenced by decreased sperm functional parameters of epididymal sperm count, viability, and motility, and increased sperm abnormalities manifested in the head, tail, and midpiece of sperm. This observation agrees with previous findings in our laboratory and other laboratories (Owumi, Ijadele, et al, 2020;Sharma et al, 2020) that sperm parameters evaluated in this study were negatively affected by AFB 1 . Interestingly, CA abrogated AFB1-induced reproductive toxicity by increasing the indices of sperm functionality and decreasing the index of sperm abnormalities in the experimental animals.…”

Biochemical and histological alterations of doxorubicin‐induced neurotoxicity in rats: Protective role of luteolin

“…Based on our findings, we conclude that the protective effect of LUT against DOX-induced neurotoxicity is via a combination of LUT scavenging ability of ROS/RNS, inhibition of proapoptotic proteins and markers of inflammations as earlier observed in our previous studies on other target organs. [31,54,55] Our previous findings are indicative of LUT readily bioavailability that can therefore confer protection against oxidative damage in various organs. cerebrum and hypothalamus weight (Table 1), similar to another study.…”

“…[74] LUT coadministration, improved In conclusion, previous studies have demonstrated that LUT could ameliorate systemic toxicities caused by DOX-based chemotherapy. [18,31,[72][73][74] The BBB penetrability of LUT, together with its neuroprotective and anti-inflammatory effects, makes it an ideal small molecule to investigate the prospect of its ability to protect against or reverse DOX-induced cognitive dysfunction, a serious side-effect that has not garnered much attention as the wellestablished cardiotoxic effects of DOX. We presently demonstrate that DOX treatment can result in toxic outcomes in a male rat's brain.…”

“…There are many previous studies on the protective effect of LUT against DOX toxicity on the heart, breast cancer cell line, [15][16][17] testicle, and lungs. [18] Therefore, we hypothesize that the administration of LUT, a member of the flavonoid family, may offer protection against DOX-induced neurotoxicity. Earlier studies have shown that LUT exhibits several pharmacological effects inter alia: neuroprotective, antioxidant, anti-inflammatory, apoptotic, and anticancer activities.…”

N ‐acetyl cysteine co‐treatment abates perfluorooctanoic acid‐induced reproductive toxicity in male rats

“…Lipid peroxidation was determined by quantifying thiobarbituric acid reactive substances (TBARS) in the testicular and epididymal homogenates using the previously reported method of Buege and Aust (Buege & Aust, 1978;Owumi, Ijadele, et al, 2020). Test samples (40 µl) was mixed with 0.15 M Tris-KCl buffer (160 µl; pH: 7.4) containing 30% TCA (50 µl).…”