Mohammed F. Alotaibi

Retraction for the article Umbelliferone Inhibits Spermatogenic Defects and Testicular Injury in Lead-Intoxicated Rats by Suppressing Oxidative Stress and Inflammation, and Improving Nrf2/HO-1 Signaling

Cisplatin (CIS) is an effective chemotherapeutic agent against different cancers. The use of CIS is associated with acute lung injury (ALI) and other adverse effects, and oxidative stress and inflammation were implicated in its toxic effects. Candesartan (CAN), an angiotensin II (Ang II) receptor blocker, showed beneficial effects against oxidative stress and inflammation. Therefore, this study investigated the potential of CAN to prevent CIS-induced oxidative stress, inflammation, and lung injury in rats, pointing to the involvement of TLR4/NF-κB, JAK1/STAT3, PPARγ, and Nrf2/HO-1 signaling. The rats received CAN (5 mg/kg) for 10 days and were challenged with a single dose of CIS (7 mg/kg) on day 7. CIS caused injury to the alveoli and the bronchial tree, increased lipid peroxidation, nitric oxide, myeloperoxidase, TLR-4, NF-κB p65, iNOS, TNF-α, IL-6, IL-1β, and caspase-3, and decreased cellular antioxidants and IL-6 in the lungs of rats. CAN effectively prevented tissue injury, suppressed TLR-4/ NF-κB signaling, and ameliorated oxidative stress, inflammatory markers, and caspase-3 in CIS-administered rats. CAN enhanced antioxidants and IL-10, decreased Ang II, increased Ang (1–7), suppressed the phosphorylation of JAK1 and STAT3, and upregulated SOCS3 in CIS-administered rats. These effects were associated with the downregulation of Keap1 and enhanced Nrf2, GCLC, HO-1, and PPARγ. In conclusion, CAN prevented CIS-induced lung injury by attenuating oxidative stress, suppressing TLR-4/NF-κB and JAK1/STAT3 signaling, Ang II, and pro-inflammatory mediators, and upregulating PPARγ, and Nrf2/HO-1 signaling.

Introduction: Lead (Pb) is an environmental toxic metal that threatens human health. Umbelliferone (UMB) is a coumarin with known medicinal and protective properties against cytotoxicity. This study explored the ameliorative effect of UMB against Pb-induced testicular toxicity in rats, focusing on steroidogenesis, oxidative stress and inflammation. Materials and Methods: Rats received lead acetate (50 mg/kg) and UMB (25, 50 or 100 mg/kg) via oral gavage for 4 weeks. Results: Pb-intoxicated rats exhibited testicular tissue injury and decreased serum levels of LH, FSH and testosterone. The count, viability, motility and normal morphology of the sperms were decreased accompanied with downregulated steroidogenesis markers in Pb-induced group. UMB prevented testicular injury, increased serum levels of LH, FSH and testosterone, upregulated steroidogenesis markers and improved the semen quality. In addition, UMB attenuated oxidative stress and oxidative DNA damage, downregulated the expression of pro-inflammatory mediators and Bax, boosted antioxidant defenses and Bcl-2, and upregulated Nrf2/HO-1 signaling in Pb-intoxicated rats. Conclusion: UMB prevents Pb-induced testicular injury by suppressing oxidative damage, inflammation and cell death, and boosting antioxidant defenses, Nrf2/HO-1 signaling and pituitary-gonadal axis. Thus, UMB may represent a protective and cost-effective agent against Pb testicular toxicity, pending further investigations to elucidate other underlying mechanisms.

Continuous oxytocin exposure to augment labor contractions may cause receptor desensitization and further reduce the uterine response to oxytocin, resulting in an increased risk of uterine atony. This study aimed to investigate and compare the uterine response to continuous and intermittent oxytocin stimulation. We hypothesized that intermittent brief episodes of oxytocin separated by recovery periods rather than continuous oxytocin application improves subsequent uterine contractions. Myometrial strips were isolated from term-pregnant rats (22 days of gestation; n = 11), mounted in tissue bath chambers, and exposed to continuous oxytocin (5 nM) for 2 h or 6 repeated episodes of 10-min oxytocin exposure (5 nM) separated by 10 min of recovery period in Krebs solution. Contractile parameters (force amplitude, frequency, and integral force) significantly decreased during continuous oxytocin exposure compared with control (n = 11; P < 0.01). Interestingly, myometrial contractility significantly increased during subsequent short intermittent oxytocin exposure which was sustained for 6 h compared with control or continuous exposure (n = 11; P < 0.01). Brief intermittent oxytocin stimulations resulted in better uterine response and improved contractile force than continuous exposure, which may be attributed to attenuation of receptor desensitization or recovery of oxytocin receptor function following intermittent exposure. These findings would help maintain adequate strong contractions to avoid postpartum bleeding.

Puberty is a physiological event involving the attainment of reproductive capability and complete development of sexual and physical organs. Changing from childhood to adulthood is a complex process and is tightly controlled by interconnection pathways at the level of the hypothalamus which can be influenced by environmental, psychosocial, and endocrine factors. Although various mechanisms underlying the onset of normal puberty have been investigated in humans and animals, the exact molecular mechanisms thereof remain unclear. The aim of this review is to summarize the current state of knowledge and provide a synoptic overview about the physiology of puberty in adolescent boys and girls, and describe pathological disorders affecting its onset.

Hypoxic preconditioning ameliorates endometrial and myometrial damage and improves uterine function following prolonged hypoxia in nonpregnant rats

To assess the in vitro effect of hydrogen peroxide (H[2] O[2] ) on uterine contractions in pregnant and non-pregnant rats.The study was performed at the Department of Physiology, College of Medicine, King Saud University from December 2016 to October ...