Stromal cell-derived factor-1α predominantly mediates the ameliorative effect of linagliptin against cisplatin-induced testicular injury in adult male rats

Elrashidy, Rania A.; Hasan, Rehab A.

doi:10.1016/j.cyto.2020.155260

Cited by 10 publications

(16 citation statements)

References 56 publications

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“…Cisplatin (CP) has been used for more than 50 years in many cancers such as breast, ovarian, testicular and bladder cancers (Sun et al, 2019). Although CP is a strong anti‐tumour, it causes damage to the kidney, liver, intestine and testis (Elrashidy & Hasan, 2020). The mechanism of action of CP binds to purine bases of DNA, causing DNA strand breakage and ultimately cell death (Mesbahzadeh et al, 2021) In addition, apoptosis, inflammation and oxidative stress are the major reported mechanisms of toxic effects of CP in tissues (Eren et al, 2020; Fallahzadeh et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Sinapic acid ameliorates cisplatin‐induced disruptions in testicular steroidogenesis and spermatogenesis by modulating androgen receptor, proliferating cell nuclear antigen and apoptosis in male rats

Demir

Altındağ

2022

Andrologia

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The chemotherapeutic cisplatin, which is widely used in many cancer types, causes testicular toxicity. Sinapic acid has many therapeutic effects such as antioxidant, anti‐inflammatory and antihyperglycaemic. This study aimed to investigate the improving effects of sinapic acid in cisplatin‐induced testicular toxicity. Twenty‐eight rats were distributed into 4 groups. Control group: saline was applied intraperitoneal. Cisplatin group: A single dose of 7 mg/kg of cisplatin was injected into rats. Cisplatin +Sinapic acid group: 3 days after a single dose of 7 mg/kg cisplatin was injected, 25 mg/kg of sinapic acid was given for 7 days. Sinapic acid group: rats were received 25 mg/kg/day of sinapic acid. Numerical density of spermatogonium, Leydig and volume density of germinal epithelial were calculated. Caspase‐3, Bcl‐2, AR and PCNA expressions in testis were evaluated and testosterone and LH levels were measured. Cisplatin application decreased the numerical density of spermatogonium and Leydig, volume density of germinal, epididymal sperm count, testosterone, LH and the expressions of Bcl‐2, AR and PCNA in testis. However, sinapic acid treatment significantly restored the parameters of our study. The results of the present study revealed that cisplatin can cause male reproductive toxicity and sinapic acid can have improving effects against cisplatin‐induced male reproductive toxicity.

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Section: Introductionmentioning

confidence: 99%

Sinapic acid ameliorates cisplatin‐induced disruptions in testicular steroidogenesis and spermatogenesis by modulating androgen receptor, proliferating cell nuclear antigen and apoptosis in male rats

Demir

Altındağ

2022

Andrologia

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“…The anti‐tumour effect of CP, a DNA‐alkylating molecule, prevents the replication and transcription of DNA by breaking the DNA double strands (Ahmed et al., 2011). However, CP has side effects such as ototoxicity, nephrotoxicity, neurotoxicity and testicular toxicity, as well as significant anti‐tumour effects (Elrashidy & Hasan, 2020). It has been determined that oxidative stress, inflammation and ischaemic injury are pathological conditions caused by CP toxicity in tissues (Eren et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

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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“…Inhibition of the dipeptidyl peptidase-4 (DPP-4) has been proven to be an effective tool for suppression of inflammatory responses in several pathological models of testicular injury, such as cisplatin [ 21 ] and doxorubicin [ 22 ] induced testicular damage. In these models, the beneficial actions of DPP-4 inhibition against male reproductive dysfunction have been characterized, including improvement of testosterone levels, sperm deformity, and testicular histopathology.…”

Section: Introductionmentioning

confidence: 99%

“…The enhancement of SDF-1α has been associated with favorable testicular outcomes in toxicant-induced testicular injury. This can be linked to the intensified testicular tissue repair and regeneration by the mobilized stem cells to the damaged site [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Repositioning Linagliptin for the Mitigation of Cadmium-Induced Testicular Dysfunction in Rats: Targeting HMGB1/TLR4/NLRP3 Axis and Autophagy

et al. 2022

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Cadmium, a ubiquitous environmental toxicant, disrupts testicular function and fertility. The dipeptidyl peptidase-4 inhibitor linagliptin has shown pronounced anti-inflammatory and anti-apoptotic features; however, its effects against cadmium-evoked testicular impairment have not been examined. Herein, the present study investigated targeting inflammation, apoptosis, and autophagy by linagliptin for potential modulation of cadmium-induced testicular dysfunction in rats. After 60 days of cadmium chloride administration (5 mg/kg/day, by gavage), testes, epididymis, and blood were collected for analysis. The present findings revealed that linagliptin improved the histopathological lesions, including spermatogenesis impairment and germ cell loss. Moreover, it improved sperm count/motility and serum testosterone. The favorable effects of linagliptin were mediated by curbing testicular inflammation seen by dampening of HMGB1/TLR4 pathway and associated lowering of nuclear NF-κBp65. In tandem, linagliptin suppressed the activation of NLRP3 inflammasome/caspase 1 axis with consequent lowering of the pro-inflammatory IL-1β and IL-18. Jointly, linagliptin attenuated testicular apoptotic responses seen by Bax downregulation, Bcl-2 upregulation, and suppressed caspase 3 activity. With respect to autophagy, linagliptin enhanced the testicular autophagy flux seen by lowered accumulation of p62 SQSTM1 alongside upregulation of Beclin 1. The observed autophagy stimulation was associated with elevated AMPK (Ser487) phosphorylation and lowered mTOR (Ser2448) phosphorylation, indicating AMPK/mTOR pathway activation. In conclusion, inhibition of testicular HMGB1/TLR4/NLRP3 pro-inflammatory axis and apoptosis alongside stimulation of autophagy were implicated in the favorable actions of linagliptin against cadmium-triggered testicular impairment.

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Stromal cell-derived factor-1α predominantly mediates the ameliorative effect of linagliptin against cisplatin-induced testicular injury in adult male rats

Cited by 10 publications

References 56 publications

Sinapic acid ameliorates cisplatin‐induced disruptions in testicular steroidogenesis and spermatogenesis by modulating androgen receptor, proliferating cell nuclear antigen and apoptosis in male rats

Sinapic acid ameliorates cisplatin‐induced disruptions in testicular steroidogenesis and spermatogenesis by modulating androgen receptor, proliferating cell nuclear antigen and apoptosis in male rats

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

Repositioning Linagliptin for the Mitigation of Cadmium-Induced Testicular Dysfunction in Rats: Targeting HMGB1/TLR4/NLRP3 Axis and Autophagy

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