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    Chronic Water-Pipe Smoke Exposure Induces Injurious Effects to Reproductive Systemin Male Mice
    (Frontiers Media Sa, 2017) Ali, Badreldin H.; Al Balushi, Khalid A.; Ashique, Mohammed; Shalaby, Asem; Al Kindi, Mohammed A.; Adham, Sirin A.; Karaca, Turan
    There is a global increase in the popularity of water-pipe tobacco smoking including in Europe and North America. Nevertheless, little is known about the male reproductive effects of water-pipe smoke (WPS), especially after long-term exposure. Here, we assessed effects of WPS exposure (30min/day) in male mice for 6 months. Control mice were exposed to air-only for the same period of time. Twenty-four hours after the last exposure, testicular histopathology, and markers of inflammation and oxidative stress, and the tyrosine-protein kinase vascular endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone (LH) concentrations were also measured. Chronic WPS exposure induced a significant decrease of testosterone and estradiol, and a slight but significant increase of LH. Glutathione reductase, catalase, and ascorbic acid were significantly decreased following WPS exposure. Plasma concentration of leptin was significantly decreased by WPS exposure, whereas that of tumor necrosis factor a and interleukin 6 was significantly increased. Histopathological analysis of the testes revealed the presence of a marked reduction in the diameter of the seminiferous tubules with reduced spermatogenesis. Transmission electron microscopy examination showed irregular thickening and wrinkling of the basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1 was overexpressed in the testis of the mice exposed to WPS and was not detected in the control. The urine concentration of cotinine, the predominant metabolite of nicotine, was significantly increased in the WPS-exposed group compared with the control group. We conclude that chronic exposure to WPS induces damaging effects to the reproductive system in male mice. If this can be confirmed in humans, it would be an additional concern to an already serious public health problem, especially with the increased use ofWPS use all over the world, especially in young adults.
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    The effect of swimming exercise on adenineinduced kidney disease in rats, and the influence of curcumin or lisinopril thereon
    (Public Library Science, 2017) Ali, Badreldin H.; Karaca, Turan; Al Suleimani, Yousuf; Al Za'abi, Mohammed; Al Kalbani, Jamila; Ashique, Mohammed; Nemmar, Abderrahim
    Patients with chronic kidney disease (CKD) have been reported to benefit from different types of exercises. It has also been shown that the ACE inhibitor lisinopril, and the natural product curcumin are also beneficial in different models of CKD in rats. We assessed the influence of moderate swimming exercise (SE) on rats with adenine- induced CKD, and tested the possible effects of lisinopril and/or curcumin thereon using several physiological, biochemical, histopathological and immunohistochemical parameters. Rats (either sedentary or subjected to SE) were randomly divided into several groups, and given for five weeks either normal food or food mixed with adenine (0.25% w/w) to induce CKD. Some of these groups were also concomitantly treated orally with curcumin (75 mg/kg), or lisinopril (10 mg/kg) and were subjected to moderate SE (45 min/day three days each week). Rats fed adenine showed the typical biochemical, histopathological signs of CKD such as elevations in blood pressure, urinary albumin / creatinine ratio, and plasma urea, creatinine, indoxyl sulfate and phosphorus. SE, curcumin or lisinopril, given singly, significantly ameliorated all the adenine-induced actions. Administering curcumin or lisinopril with SE improved the histopathology of the kidneys, a salutary effect not seen with SE alone. Combining SE to the nephroprotective agents' curcumin or lisinopril might offer additional nephroprotection.
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    The effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on gentamicin nephrotoxicity in mice
    (Elsevier France-Editions Scientifiques Medicales Elsevier, 2018) Al Suleimani, Yousuf M.; Abdelrahman, Aly M.; Karaca, Turan; Manoj, Priyadarsini; Ashique, Mohammed; Nemmar, Abderrahim; Ali, Badreldin H.
    This study aimed at investigating the possible ameliorative effects of sitagliptin in mice with gentamicin (GEN) nephrotoxicity. Sitagliptin was given to the animals at an oral dose of 10 mg kg(-1) per day for 10 days, and in some of these mice, GEN was injected intraperitoneally at a dose of 100 mg kg(-1) per day during the last seven days of the treatment. Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically by measuring several indices in plasma, urine and renal cortex homogenates. GEN treatment induced nephrotoxicity as evidenced by significantly (P < 0.0001) increasing the plasma concentrations of urea, creatinine, circulatory cytokines, cystatin C, sclerostin, and TNF alpha. Treatment with GEN also significantly elevated urinary N-acetyl-beta-D glucosaminidase (NAG) concentration (P < 0.0001). Moreover, GEN caused significant increase in oxidative stress in the kidneys (P < 0.0001). Histopathological examination revealed massive tubular injury, necrosis, infiltration of inflammatory cells and intraluminal hyaline casts in mice treated with GEN. Sitagliptin alone did not significantly affect any of the indices measured. However, concomitant treatment with sitagliptin and GEN significantly mitigated most of the nephrotoxic actions of GEN. Pending further studies, sitagliptin may potentially be useful as a nephroprotectant agent.
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    Potassium bromate-induced kidney damage in rats and the effect of gum acacia thereon
    (E-Century Publishing Corp, 2018) Ali, Badreldin H.; Al Za'abi, Mohammed; Karaca, Turan; Al Suleimani, Yousuf; Al Balushi, Khalid A.; Manoj, Priyadarsini; Ashique, Mohammed
    Potassium bromate (KBrO3) is used in many countries in cosmetic and food industries. In this work, we investigated in male Sprague-Dawley rats, the effect of four graded oral doses of KBrO3 (5, 15, 45 and 135 mg/kg/day for 28 days) on renal function tests, inflammation, oxidative damage, and apoptosis, as well as on histopathology, using several traditional and novel renal injury biomarkers in plasma, urine and renal tissues. We also tested the possible ameliorative action of the renoprotective prebiotic agent gum acacia (GA) on the actions of KBrO3 when given concomitantly with it in the drinking water at a concentration of 15% w/v. Taken together, the results indicated that treatment with KBrO3 at the 45 and 135 mg/kg doses caused a significant dose-dependent nephrotoxicity, as evident by the measured renal structural and functional indices and biomarkers of toxicity. GA co-treatment significantly abated most of the indices and biomarkers of the renal toxicity caused by KBrO3, suggesting a beneficial effect and its possible inclusion in edible products where KBrO3 is still used.