Acacia hydaspica ethyl acetate extract protects against cisplatin-induced DNA damage, oxidative stress and testicular injuries in adult male rats

Afsar, Tayyaba; Razak, Suhail; Khan, Muhammad Rashid; Almajwal, Ali

doi:10.1186/s12885-017-3898-9

Cited by 62 publications

(60 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found a CP-mediated decrease in peripheral blood testosterone concentration, likely resulting in a decrease in testosterone concentration in testes, which is fundamentally consistent with previous reports [43,44,53]. It is now accepted that Leydig cells produce testosterone in response to LH and that testosterone acts as a paracrine factor that diffuses into the seminiferous tubules and is required for maintaining spermatogenesis [54].…”

Section: Discussionsupporting

confidence: 92%

“…As such, MDA is used as an indirect indicator of ROS based on the high reactivity and short half-life of ROS making it difficult to quantify [41,42]. Our findings were substantially consistent with previous reports showing that CP treatment causes adverse effects in the testis by inducing oxidative stress and apoptosis [43][44][45][46][47][48][49].…”

Section: Discussionsupporting

confidence: 86%

“…Similar to RLN, melatonin mitigates the deleterious side effects of CP by exerting antioxidant and antiapoptotic effects in testes, with increased sperm count and motility and decreased abnormal forms [57]. Additionally, dietary antioxidants, such as lycopene [45], Roselle and Ginger [47], royal jelly [48], and rutin [49], as well as plant [44] or fruit extracts [46], have been reported to exert protective effects against CP-induced testicular toxicity. Therefore, RLN might represent a potentially effective drug option for use in cisplatin chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of relaxin for cisplatin-induced testicular dysfunction and epididymal spermatotoxicity

Kohsaka

Minagawa

Morimoto

et al. 2020

Basic Clin. Androl.

View full text Add to dashboard Cite

Background: Cisplatin (CP) is an extremely effective anticancer agent widely used to treat various cancer types, however, the potential side effects include testicular dysfunction. This study was to investigate, using a rat model of CP-induced testicular dysfunction, the protective effects of relaxin (RLN) against oxidative stress, testicular function, histological damage, spermatogenesis, germ-cell apoptosis, and sperm output, and to explore the usefulness of RLN as a potential protective drug for use with CP in chemotherapeutic treatments. Methods: Sprague-Dawley male rats were used, which were divided into three groups: sham control, CP, and CP + RLN. Porcine RLN (500 ng/h) or saline was infused for 5 days using an implanted osmotic mini-pump following intraperitoneal injection of CP (6 mg/kg). RLN dose was chosen based on previous studies showing that it resulted in serum relaxin levels comparable to those in rats at the middle of pregnancy. At 5 days after CP administration, samples were collected and assessment of testicular histopathology, germ-cell apoptosis, oxidative stress, lipid peroxidation, and sperm quality was performed as main measures. Results: The testicular CP model showed reduced testis weight and significantly decreased spermatogenesis scores. Additionally, CP administration induced a 4.6-fold increase in the apoptotic index associated with a significant increase in oxidative stress and upregulation of pro-apoptotic Casp3 and downregulation of anti-apoptotic Bcl2 levels, resulting in a marked reduction in sperm concentration. However, RLN administration caused a significant reduction in CP-mediated damage by attenuating oxidative stress and cell apoptosis. RLN administration efficiently scavenged ROS via the activation of SOD, CAT, and GPx and upregulation of GSH to prevent lipid peroxidation and decreased apoptosis by altering Bcl2 and Casp3 expression, thereby reducing histopathological damage and restoring spermatogenesis. Furthermore, RLN ameliorated attenuated sperm motility in the cauda epididymis resulting from CP treatment. Conclusions: This study clearly indicates that RLN exerts a protective effect against CP-induced testicular damage through attenuation of oxidative stress and suppression of apoptosis. Our findings suggest RLN as a potentially efficacious drug for use with cisplatin chemotherapy in order to ameliorate CP-induced side effects and testicular injury adversely affecting spermatogenesis, sperm quality, and oxidative-stress parameters.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of relaxin for cisplatin-induced testicular dysfunction and epididymal spermatotoxicity

Kohsaka

Minagawa

Morimoto

et al. 2020

Basic Clin. Androl.

View full text Add to dashboard Cite

show abstract

“…Chromosomal abnormalities in spermatozoa and temporary or permanent azoospermia are associated side effects of CP treatment. These side effects are attributed to oxidative and nitrosative damage generated by CP [ 7 ]. Physiological and biochemical disturbance is caused by redox imbalance and increase in lipid peroxidation lead to germ cell apoptosis [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Ameliorative effects of rutin against cisplatin-induced reproductive toxicity in male rats

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundCisplatin (CP) or cis-diammine dichloroplatinum (II) is a platinum based standard antineoplastic drug which is used against variety of solid tumors and neoplasms. The present study aimed to evaluate the shielding effects of rutin against CP induced testicular toxicity in rats.Methods28 male rats were divided into four groups. First group was given saline orally while second group received intra-peritoneal (i.p) injection of cisplatin (7 mg/kg) on day first and received saline for next 13 days. Third group received i.p injection of cisplatin at day one and treated with rutin (75 mg/kg) orally for next 13 days. Fourth group was treated with rutin orally for 13 days. Animals were sacrificed on 14th day and reproductive organs were analyzed for various parameters.ResultsCisplatin treatment resulted in a significant decrease in daily sperm production, decrease in head length and % DNA in head, reduction of epithelial cell height, tubular diameter, reduction of the number of spermatogonia, spermatocytes and spermatids, increase in the thiobarbituric acid reactive substances (TBARS) and oxidative stress in testicular tissues, and change of the intra-testicular testosterone concentrations. Rutin co-treatment resulted in reversing cisplatin effect on DNA damage, sperm count, histological and biochemical parameters.ConclusionThese results indicated that rutin co-treatment could ameliorate cisplatin-induced reproductive toxicity in male rats.

show abstract

“…The previous studies reported that the DNA damage is firmly linked to teratogenicity ( Yang et al, 2014 ; Si et al, 2017 ; Wani et al, 2017 ) and reproductive toxicity ( Lin et al, 2014 ; Yang et al, 2014 ; Afsar et al, 2017 ; Adana et al, 2018 ). QdNOs, acting as an inhibitor of DNA synthesis, induced genotoxicity in the bacteria and mammalian cells ( Cheng et al, 2015 ; Liu et al, 2016 , 2017a ; Wang et al, 2016a ), suggesting that DNA damage may involve in the teratogenicity and reproductive toxicity mediated by MEQ.…”

Section: Discussionmentioning

confidence: 99%

The Reproductive Toxicity of Mequindox in a Two-Generation Study in Wistar Rats

Liu

Lei

et al. 2018

Front. Pharmacol.

View full text Add to dashboard Cite

Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), has been extensively used as a synthetic antibacterial agent. To evaluate the reproductive toxicity of MEQ, different concentrations of MEQ were administered to Wistar rats by feeding diets containing 0, 25, 55, 110, and 275 mg/kg, respectively. Each group consisting of 25 males and 25 females (F0) was treated with different concentrations of MEQ for 12-week period time, prior to mating and during mating, gestation, parturition and lactation. At weaning, 25 males and 25 females of F1 generation weanlings per group were randomly selected as parents for the F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. The number of live litter and indexes of mating and fertility were significantly decreased in the F1 and F2 generation at 110 and 275 mg/kg groups. Significant decrease in pup vitality during lactation was observed in F1 litter at 275 mg/kg group, in F2 litter at 55, 110, and 275 mg/kg groups. A downward trend in the body weights was observed in F1 pups at 55, 110, and 275 mg/kg MEQ groups, and in F2 pups at 110 and 275 mg/kg MEQ groups. The changed levels of ALT, AST, CREA, BUN, UA, Na, and K were noted in the serum of rats. The histopathologic examination showed that MEQ induced toxicity in the liver, kidney, adrenal, uterus and testis. The no-observed-adverse-effect level (NOAEL) for reproduction toxicity of MEQ was 25 mg/kg diet. The malformations and severe maternal toxicity of MEQ caused adverse effects on the conceptus and embryo, which result in fetal malformations and fetal deaths. In summary, the present study showed that MEQ induced maternal, embryo and reproductive toxicities as well as teratogenicity in rats.

show abstract

Acacia hydaspica ethyl acetate extract protects against cisplatin-induced DNA damage, oxidative stress and testicular injuries in adult male rats

Cited by 62 publications

References 62 publications

Efficacy of relaxin for cisplatin-induced testicular dysfunction and epididymal spermatotoxicity

Efficacy of relaxin for cisplatin-induced testicular dysfunction and epididymal spermatotoxicity

Ameliorative effects of rutin against cisplatin-induced reproductive toxicity in male rats

The Reproductive Toxicity of Mequindox in a Two-Generation Study in Wistar Rats

Contact Info

Product

Resources

About