Epigallocatechin-gallate attenuates rapamycin exacerbated high fat diet-induced autophagy, hormonal dysregulation, testicular and brain oxidative stress, and neurochemical changes in rats

Onyekweli, Chinedu Charles; Ben-Azu, Benneth; Oyovwi, O. Mega; Nwangwa, E. Kingsley; Ovuakporaye, I. Simon; Moke, Goodies Emuesiri; Agbonifo-Chijiokwu, Ejime; Onome, B. Oghenetega; Emojevwe, Victor; Rotu, A. Rume

doi:10.1016/j.fct.2023.114340

Cited by 5 publications

(1 citation statement)

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“…It is anticipated that future research on the reproductive anomalies induced by CP will reference the success rates of previous studies as a benchmark. To mitigate its cytotoxic effects, various antioxidant supplements, such as taurine, 69-72 quercetin, 71,73,74 D-ribose-L-cysteine, 75,76 Lutein, 77 Coenzyme Q10, 67,70,78,79 N-acetylcysteine, zinc sulfate, 80,81 Kolaviron, 82 Arjunolic acid, 83,84 Epigallocatechin-gallate, 85 Diosmin, 86 S-allylcysteine, 87 melatonin, 88 Rutin, 89 diallyl disulfide, 90 ascorbic acid, 91 vitamin E, 92 Rosmarinic, 93 and DL-alpha-lipoic acid 94 could serve as therapeutic adjuncts for preventing the reproductive anomalies caused by CP. Thus, combining drug delivery with a potent antioxidant agent may present a viable approach to mitigate the side effects of CP.…”

Section: Future Directionsmentioning

confidence: 99%

Cytotoxic Properties of Cyclophosphamide: A Focus on Its Mechanistic Impacts on Male Gonadal Functions

Olowe,

Oyovwi,

Nwangwa

et al. 2024

J Explor Res Pharmacol

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Cyclophosphamide (CP) is a potent chemotherapeutic agent utilized in the treatment of various types of cancer. However, in addition to its efficacy in combating cancer, CP also has severe side effects, including damage to male gonadal functions. This paper aims to explore the cytotoxic properties of CP and its mechanistic impacts on male gonadal functions. The search strategy was conducted using several reviewed articles indexed in PubMed, Science Direct, EBSCO, Scopus, Cochrane Library, Sage Journals, and Google Scholar. CP is an alkylating agent that damages cancer cell DNA, inhibiting growth and division. It also affects healthy cells, leading to severe cytotoxicity. In male gonadal tissues, CP damages germ cells, Leydig cells, and Sertoli cells, causing decreased sperm count, testosterone levels, and disruption of the blood-testis barrier. The metabolism of CP in the liver generates reactive oxygen species, leading to oxidative damage and cell death. Moreover, CP also affects the hypothalamic-pituitary-gonadal axis, regulating male gonadal functions. CP disrupts the production and secretion of gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone, resulting in a decrease in testosterone levels and impaired spermatogenesis. Additionally, CP exerts its cytotoxic effects by inhibiting the proliferation and differentiation of germ cells, leading to a decrease in sperm production. It also affects Leydig cells, which are responsible for the production of testosterone, thus decreasing testosterone levels. In conclusion, CP exhibits potent cytotoxic properties that not only affect cancer cells but also severely damage male gonadal functions. The mechanisms involved in CP-induced gonadal toxicity include oxidative stress and disruption of the hypothalamic-pituitary-gonadal axis. Therefore, it is crucial to consider the potential gonadal toxicity of CP when prescribing it for cancer treatment and to closely monitor the gonadal functions of male patients

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