Protocatechuic acid inhibits testicular and epididymal toxicity associated with methotrexate in rats

Abstract

We examined the effect of protocatechuic acid (PCA) on methotrexate (MTX)-induced testicular and epididymal toxicity in Wistar rats, treated with MTX (20 mg/kg) alone or in combination with PCA (25 and 50 mg/kg) body weight for a week. PCA significantly abated MTX-mediated increase in reactive oxygen and nitrogen species generation and lipid peroxidation as well as enhances glutathione balance and antioxidant enzymes in the testes and epididymis of treated animals. PCA suppressed MTX-mediated increases in interleukin-1β, tumour necrosis factor alpha and caspase-3 activity in treated animals. Additionally, PCA treatment mediated increases in luteinising and follicle-stimulating hormones, prolactin and testosterone levels with marker enzymes of testicular function, accompanied with increase in sperm functionality in treated animals. Conclusively, PCA may serve as potential supplementation, enhancing reproductive health in males undergoing MTX therapy. K E Y W O R D Sapoptosis, methotrexate, oxido-inflammation, protocatechuic acid, reproductive toxicity

Salubrious effects of a vermiculite–cellulose‐based bionanocomposite on oxidative stress indices and histomorphology of male Wistar rats

“…The association between testicular dysfunction and free radical‐induced oxidative stress has been pointed out by other researchers (Asadi, Bahmani, Kheradmand, & Rafieian‐Kopaei, ; Njoku, Abarikwu, Uwakwe, & Mgbudom‐Okah, ; Owumi, Ochaoga, Odunola, & Farombi, ). Reactive oxygen species (ROS) can be propagated via the deliberate or unwitting biological activities of specific oxidases and cytochrome P450 superfamily (Kaur, Kaur, & Bansal, ).…”

Selenium attenuates diclofenac‐induced testicular and epididymal toxicity in rats

“…Testicular activities of LDH, ALP and ACP are important in the maintenance of normal germ cell growth and phosphorylative role in glucose usage by germ cells during spermatogenesis (Akhigbe & Ajayi, 2020; Motawi, Sadik, & Refaat, 2010; Rizk, Zaki, & Mina, 2014), while G6PD is essential for providing reducing equivalent necessary for steroidogenesis (Aly & Khafagy, 2014). The decrease in serum testosterone and LH was accompanied by a clear decrease in testicular activities of ALP, ACP, G6PD and LDH in diclofenac‐treated rats signifies impairment in the synthesis or release of hormones and inhibition of marker enzyme activities vital for spermatogenesis (Adedara, Okpara, et al, 2019; Owumi, Ochaoga, Odunola, & Farombi, 2019). However, an increase in serum testosterone and LH and enzymes marker of testicular function in rats treated with diclofenac and selenium revealed advantageous effects of selenium on diclofenac‐induced reproductive toxicity.…”

Ginkgo biloba Extract Attenuates Methotrexate-Induced Testicular Injury in Rats: Cross-talk Between Oxidative Stress, Inflammation, Apoptosis, and miRNA-29a Expression

“… 9 Although the exact mechanism through which MTX could induce testicular injury is not fully investigated, it was documented that oxidative stress, inflammatory cytokines, and apoptotic cascades have been involved. 10 , 11 …”

“…Moreover, the release of pro-inflammatory cytokines like interleukin-6 (IL-6) and IL-1β along with cell death through apoptotic cascades was also documented in the pathophysiology of MTX-induced testicular injury. 10 , 13 , 15 Apoptosis is known as a process of programmed cell death and regulated by the family members of bcl-2 which has been documented to be involved in the testicular apoptosis. 16 - 18 Bcl-2 has been reported to inhibit apoptosis and prolong cell survival while bcl-2 associated x protein (Bax) could block the capability of bcl-2 in inhibiting apoptosis and could be considered as an apoptosis regulator.…”