Tert-butylhydroquinone attenuates doxorubicin-induced dysregulation of testicular cytoprotective and steroidogenic genes, and improves spermatogenesis in rats

Ujah, Godwin Adakole; Nna, Victor Udo; Suleiman, Joseph Bagi; Eleazu, Chinedum; Nwokocha, Chukwuemeka R.; Rebene, Joy Assima; Imowo, Michael Umana; Ochui, Emmanuel; Amachree, Charlette; Udechukwu, Evarest Chigozie; Mohamed, Mahaneem

doi:10.1038/s41598-021-85026-7

Cited by 26 publications

(18 citation statements)

References 67 publications

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“…The results of the DOX group revealed a significant decrease in serum testosterone and testis index value when compared with the control group. These results were in accordance with previous reported results [4], [29]. The antineoplastic agents can disturb Leydig cells directly [30].…”

Section: Discussionsupporting

confidence: 94%

“…Although DOX is a successful cancer chemotherapeutic, side effects limit the clinical utility of DOX-based therapy, including male infertility [4] and hepatotoxicity [3]. The results of the DOX group revealed a significant decrease in serum testosterone and testis index value when compared with the control group.…”

Section: Discussionmentioning

confidence: 98%

“…However, many toxic adverse effects of DOX on organs, such as the liver and testis, have also been established [3]. DOX could impede spermatogenesis [4]. The liver is the chief detoxifying tissue; therefore, it is the target of excessive amounts of genotoxic composites and anticancer drugs including DOX.…”

Section: Introductionmentioning

confidence: 99%

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Protective Potential of Ginseng and/or Coenzyme Q10 on Doxorubicin-induced Testicular and Hepatic Toxicity in Rats

Khodir

Alafify

Omar

et al. 2021

Open Access Maced J Med Sci

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Introduction: Although doxorubicin (DOX) is a successful cancer chemotherapeutic, side effects limit the clinical utility of DOX-based therapy, including male infertility and hepatotoxicity. Objective: To evaluate the testicular and hepatoprotective effect of ginseng and/or coenzyme Q10 (CoQ10) in rats exposed to DOX and the possible underlying mechanisms. Materials and Methods: Fifty adult male albino rats were divided into (10/group), control, DOX group, DOX/Gin group, DOX/CoQ10 group and DOX/Gin+CoQ10 group. Serum testosterone, serum liver enzymes, fasting serum cholesterol and triglyceride (TG), tissue malondialdehyde (MDA), tissue superoxide dismutase (SOD), serum tumor necrosis factor-alpha (TNF-α), serum interleukin 6, serum interleukin 10, nuclear factor E2‐related factor 2 (Nrf2) gene expression in liver and testis and organ indices were measured. Histopathological and immunohistochemical assessments of apoptotic marker kaspase3 in testis and liver were also performed. Results DOX-induced toxicity is associated with a significant decrease in serum testosterone, testis and liver index values, testicular and hepatic SOD, testicular and hepatic Nrf2 gene expression and serum interleukin 10. However, there was a significant increase in serum liver enzymes, serum cholesterol and TG, testicular and hepatic MDA, serum TNF-α and serum interleukin 6 when compared with the control group. The combination of ginseng and CoQ10 resulted in significant improvement of DOX-induced changes when compared with other treated groups. Conclusion: Ginseng and CoQ10 have valuable therapeutic effects on DOX-induced testicular and hepatic toxicity via up-regulation of Nrf2 gene expression, inhibition of apoptosis, anti-oxidant, anti-inflammatory and hypolipidemic effects.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 98%

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Protective Potential of Ginseng and/or Coenzyme Q10 on Doxorubicin-induced Testicular and Hepatic Toxicity in Rats

Khodir

Alafify

Omar

et al. 2021

Open Access Maced J Med Sci

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“…This hypothesis is supported by our previous experiments that showed that MP inhibited α -glucosidase in vitro and improved pancreatic β -cell function, which culminated into increased serum insulin and decreased blood glucose level [ 5 ]. On the other hand, the direct mechanism involves scavenging free radicals, thus complementing endogenous antioxidants, and likely activating Nrf2, which is known to stimulate antioxidant gene expression [ 20 , 21 ]. Our previous experiments showed that MP, which contained large amounts of phenols and flavonoids, significantly inhibited DPPH radical, had ferric ion reducing activity and H 2 O 2 scavenging activity [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Malaysian Propolis and Metformin Synergistically Mitigate Kidney Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

et al. 2021

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Diabetic nephropathy is reported to occur as a result of the interactions between several pathophysiological disturbances, as well as renal oxidative stress and inflammation. We examined the effect of Malaysian propolis (MP), which has anti-hyperglycemic, antioxidant and anti-inflammatory properties, on diabetes-induced nephropathy. Diabetic rats were either treated with distilled water (diabetic control (DC) group), MP (300 mg/kg b.w./day), metformin (300 mg/kg b.w./day) or MP + metformin for four weeks. We found significant increases in serum creatinine, urea and uric acid levels, decreases in serum sodium and chloride levels, and increase in kidney lactate dehydrogenase activity in DC group. Furthermore, malondialdehyde level increased significantly, while kidney antioxidant enzymes activities, glutathione level and total antioxidant capacity decreased significantly in DC group. Similarly, kidney immunoexpression of nuclear factor kappa B, tumor necrosis factor-α, interleukin (IL)-1β and caspase-3 increased significantly, while IL-10 immunoexpression decreased significantly in DC group relative to normal control group. Histopathological observations for DC group corroborated the biochemical data. Intervention with MP, metformin or both significantly mitigated these effects and improved renal function, with the best outcome following the combined therapy. MP attenuates diabetic nephropathy and exhibits combined beneficial effect with metformin.

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“… 29 , 34 The increased testicular levels of TNF-α and IL-6 in the untreated CP administered rats suggests the instigation of inflammatory related pathways, which corroborates well with previous reports. 40 Antioxidant and anti-inflammatory agents have been illustrated for their protective capabilities against chemotherapy induced testicular toxicities partly or wholly due to their radicals scavenging capabilities and their modulatory roles on oxidative sensitive inflammatory pathways. 5 , 41 The decrease in testicular TNF-α and IL-6 levels following the intragastric administration of EMD suggests an improvement in the testicular proinflammatory mediator status in CP treated rats which corroborates previous reports.…”

Section: Discussionmentioning

confidence: 99%

Unravelling the Protective Effects of Emodin Against Cyclophosphamide Induced Gonadotoxicity in Male Wistar Rats

Wang

Zou

Jaisi

et al. 2021

DDDT

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Background Over the past few decades, cyclophosphamide (CP) has been extensively used as a broad-spectrum alkylating agent for the treatment of various cancers and solid tumors. However, the therapeutic actions on CP are not limited to only cancer cells, as it simultaneously exerts significant toxicities on healthy cells through the instigation of oxidative stress and oxidative damages. CP induced testicular toxicity is associated with impaired spermatogenesis, reduced sperm functionality, reproductive hormone and testicular weight. This study was aimed at unravelling the protective effects of emodin (EMD) on testicular toxicity following CP treatment. Methods Twenty-four male Wistar rats were allotted into 4 groups as normal control group (NCG), CP control group (CPCG), EMD25+CP (25 mg/kg in 5% tween 80) and EMD50+CP groups (50 mg/kg in 5% tween 80). EMD was orally administered for 35 consecutive days, while four doses of CP (100 mg/kg/week) were administered intraperitoneally from the second to fifth week of treatment. Thereafter, the animals were sacrificed and histopathological examination of the testes as well as serum/testicular biochemical assays were conducted. Results The results revealed that CP significantly impeded sperm function parameters including sperm count, viability and motility as well as decreased reproductive hormones (testosterone, LH and FSH) levels. In addition, CP enhanced testicular oxidative stress and proinflammatory markers (MDA, IL-6 and TNF-α), while simultaneously decreasing testicular antioxidant enzymes (GSH, GPx, SOD and CAT). Evidence of marked histopathological alterations was also observed in the H&E stained testicular tissues of CP treated rats. EMD significantly prevented these CP induced negative effects. Conclusion This study provides a basis for the potential use of EMD in counteracting chemotherapy induced testicular toxicity. The results further suggest that EMD testicular protective effects in CP-treated rats may be mediated through its modulatory role on oxidative stress and inflammation.

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Tert-butylhydroquinone attenuates doxorubicin-induced dysregulation of testicular cytoprotective and steroidogenic genes, and improves spermatogenesis in rats

Cited by 26 publications

References 67 publications

Protective Potential of Ginseng and/or Coenzyme Q10 on Doxorubicin-induced Testicular and Hepatic Toxicity in Rats

Protective Potential of Ginseng and/or Coenzyme Q10 on Doxorubicin-induced Testicular and Hepatic Toxicity in Rats

Malaysian Propolis and Metformin Synergistically Mitigate Kidney Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

Unravelling the Protective Effects of Emodin Against Cyclophosphamide Induced Gonadotoxicity in Male Wistar Rats

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