Tert-butylhydroquinone preserve testicular steroidogenesis and spermatogenesis in cisplatin-intoxicated rats by targeting oxidative stress, inflammation and apoptosis

Nna, Victor Udo; Ujah, Godwin Adakole; Suleiman, Joseph Bagi; Mohamed, Mahaneem; Nwokocha, Chukwuemeka R.; Akpan, Timothy Joe; Ekuma, Hope Chinaza; Fubara, Victoria Victor; Kekung-Asu, Catherine Barong; Osim, E. E.

doi:10.1016/j.tox.2020.152528

Cited by 33 publications

(26 citation statements)

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“…The generated free radicals may be responsible for the attack of electron-rich components of biological membranes, leading to their destruction and thereby jeopardizing the cellular integrity and functions [ 44 , 45 ]. In a study where furan was administered to rats, testicular MDA concentration was found to increase significantly [ 46 ], while cisplatin triggered testicular and epididymal oxidative stress in rats [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Ethylene glycol monomethyl ether-induced testicular oxidative stress and time-dependent up-regulation of apoptotic, pro-inflammatory, and oncogenic markers in rats

et al. 2020

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Ethylene glycol monomethyl ether (EGME) is a major component of paints, lacquers, inks, and automobile brake fluids. As a result, exposures to humans are inevitable. We therefore, investigated in this study, its effect on testicular cells in a time-course manner in male Wistar rats. Animals were orally administered 50 mg/kg body weight of EGME for duration of 7, 14, and 21 days. Following 7 days of the administration, levels of NO and GSH were significantly reduced, while levels of c-Myc, K-Ras, caspase-3, IL-6, TNF-α, and IL-1β were significantly increased compared with control. At the end of 14 days exposure, GPx, and SOD activities, as well as IL-10 level were significantly decreased, while levels of c-Myc, K-Ras, p53, Bax, caspase-3, IL-6, TNF-α, IL-1β, and GST activity were significantly elevated compared with control. After 21 days of EGME administration, Bcl-2, IL-10, and NO levels were significantly decreased, while levels of c-Myc, K-Ras, p53, Bax, caspase-3, IL-6, TNF-α, IL-1β, MDA and GST activity were significantly increased compared with control. After 7, 14, and 21 days of EGME administrations, testis histopathology showed severe loss of seminiferous tubules, the seminiferous epithelium revealed very few spermatocytes, spermatids, spermatogonia, spermatozoa, and Sertoli cells, while the interstitial tissue is eroded, with scanty abnormal Leydig cells, compared with the control that appeared normal. We therefore, concluded that EGME-induced testicular toxicity as a result of EGME administration could be via the disorganization of the endogenous antioxidant systems as well as up-regulation of pro-inflammatory, apoptotic and oncogenic mediators in rats.

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Section: Discussionmentioning

confidence: 99%

Ethylene glycol monomethyl ether-induced testicular oxidative stress and time-dependent up-regulation of apoptotic, pro-inflammatory, and oncogenic markers in rats

et al. 2020

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“…Bcl-2, an anti-apoptotic protein, maintains mitochondrial membrane integrity(Fouad et al 2017). Previous studies have reported that CP causes upregulation of caspase-3 and downregulation of Bcl-2(Nna et al, 2020;Kohsaka et al 2020).Similarly, Aly and Eid (2020) have reported that CP treatment increased the activity of caspase-3 and bax while decreased the activity of bcl-2 in testis. They also showed that resveratrol decreased activity of caspase-3 and bax but increased activity of bcl-2.…”

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confidence: 97%

“…Chemotherapeutic agents are considered to be among the high-risk factors of infertility(Nna et al 2020). Typically, infertility occurs after chemotherapy and radiotherapy.…”

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confidence: 99%

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Evaluation of protective effects of gallic acid on cisplatin‐induced testicular and epididymal damage

Altındağ

Meydan

2021

Andrologia

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The current study explored the bene cial effects of GA against testis and epididymis toxicity induced by CP treatment. Male rats were into 4 groups (n=7). Control (saline, intraperitoneal), Cisplatin (a single dose of 8 mg/kg/day cisplatin, intraperitoneal), Gallic acid (50 mg/kg Gallic acid orally for 10 days) and Cisplatin+Gallic acid groups. Total number of spermatogonia, Sertoli, Leydig cell and the total volume of testis, seminiferous tubule, interstitial area, and germinal epithelial thickness and numerical densities of caspase-3, Bax, Bcl-2, 8-OHdG immunopositive cells were calculated. Histopathological examination of the testis and epididymis was performed. MDA and CAT levels are measured in the testis. Also, the testosterone level was measured in the serum of the rats. As a result, a signi cant decrease was observed in all stereological data, Bcl-2 immunopositive cell number, CAT, and serum testosterone levels in the testis compared to the CP group control group, while a signi cant increase was observed in the number of caspase-3, Bax, and 8-OHdG immunopositive cells and the level of MDA. However, GA signi cantly improved these parameters. Our study reveals that GA may improve CP-induced male reproductive toxicity by reducing oxidative stress, suppressing apoptosis and DNA damage, and restoring structural and functional deterioration.

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“…Cisplatin (CP) is one of the most effective medications for the treatment of malignant diseases [ 1 ]; however, nephrotoxicity is still the major dose-limiting side effect and is observed in approximately 30% of patients [ 2 ]. Oxidative stress resulting from excessive production of reactive oxygen species (ROS) plays a critical role in CP-induced nephrotoxicity [ 3 , 4 ]. When CP enters the cell, it reacts with intracellular antioxidants, disrupts the redox balance, and interferes with the respiratory chain in mitochondria, resulting in elevated ROS [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Penetratin Analogue‐Tagged SOD1 on Cisplatin‐Induced Nephrotoxicity through Inhibiting Oxidative Stress and JNK/p38 MAPK Signaling Pathway

Wang

Lin

et al. 2021

Oxidative Medicine and Cellular Longevity

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Copper/zinc superoxide dismutase (SOD1) can clear cisplatin- (CP-) induced excessive reactive oxygen species (ROS), but exogenous SOD1 cannot enter cells because of its low biomembrane permeability. Cell-penetrating peptides (CPPs) can rapidly cross plasma membranes. This study is aimed at identifying an efficient and stable CPP-SOD1 and investigating its effects on CP-induced nephrotoxicity. We recombined SOD1 with 14 different CPPs and purified them using an NTA-Ni2+ column. In in vitro experiments, CPPs-SOD1 cell membrane penetration ability and JNK/p38 MAPK signaling pathway were evaluated using Western blotting. ROS production, mitochondrial membrane potential (MMP), and cell apoptosis were determined using flow cytometry and immunofluorescence staining in VERO and HK-2 cells. For in vivo experiments, mice were administered PSF-SOD1 for 2 h before cotreatment with a single CP injection for an additional 4 days. Blood and kidney samples were collected for renal function assessment (creatinine, urea nitrogen, histopathology, TUNEL assay, and JNK/p38 MAPK signaling pathway). Compared with TAT-SOD1, we found that PSF-SOD1 is more efficient at crossing the cell membrane and is stable after transduction into cells. Pretreatment with PSF-SOD1 inhibited CP-induced apoptosis, ROS generation, and JNK/p38 MAPK activation and restored CP-induced MMP loss in VERO and HK-2 kidney cells. Treatment of mice with PSF-SOD1 inhibited CP-induced serum creatinine, blood urea nitrogen elevation, and JNK/p38 MAPK activation. H&E staining and TUNEL assay indicated that kidney tissue damage was alleviated following PSF-SOD1 pretreatment. Overall, PSF-SOD1 ameliorated CP-induced renal damage by partially reducing oxidative stress and cell apoptosis by regulating JNK/p38 MAPK signaling pathway and might be a better cytoprotective agent than TAT-SOD1.

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Tert-butylhydroquinone preserve testicular steroidogenesis and spermatogenesis in cisplatin-intoxicated rats by targeting oxidative stress, inflammation and apoptosis

Cited by 33 publications

References 59 publications

Ethylene glycol monomethyl ether-induced testicular oxidative stress and time-dependent up-regulation of apoptotic, pro-inflammatory, and oncogenic markers in rats

Ethylene glycol monomethyl ether-induced testicular oxidative stress and time-dependent up-regulation of apoptotic, pro-inflammatory, and oncogenic markers in rats

Evaluation of protective effects of gallic acid on cisplatin‐induced testicular and epididymal damage

Protective Effect of Penetratin Analogue‐Tagged SOD1 on Cisplatin‐Induced Nephrotoxicity through Inhibiting Oxidative Stress and JNK/p38 MAPK Signaling Pathway

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