Ameliorative Effects of Gallic Acid on Cisplatin-Induced Nephrotoxicity in Rat Variations of Biochemistry, Histopathology, and Gene Expression.

BACKGROUND: Cisplatin is a powerful chemotherapeutic drug mainly used in the treatment of solid tumors. Aggregation of the drug in renal proximal tubule cells causes nephrotoxicity and renal failure. Investigations showed nephrotoxicity as Cisplatin's dose-limiting side effect. One of the Cisplatin toxicity mechanisms is generation of reactive oxygen species, which leads to oxidative stress and renal damage. The purpose of this study was evaluation of the modulating effects of Gallic acid on Cisplatin-induced variations including Caspase-3 and Clusterin expression and histopathological and biochemical parameters in adult male Wistar rats. METHOD: Rats were kept under standard condition of temperature, light, and humidity. The animals were divided into 4 groups: GpI: control group (received distilled water for 10 days); GpII: Gallic acid (alone) (50 mg/kg bw, once a day for 10 days); GpIII: Cisplatin (alone), single dose (6 mg/kg bw, I.P. on 5th day of study); GpIV: Gallic acid (50 mg/kg bw, once a day for 10 days) and also injected with single dose of Cisplatin (6 mg/kg bw, I.P., on 5th day of study). After 10 days, all rats were anaesthetized and plasma collected to estimate urea, creatinine, and uric acid. The right kidneys were removed for the study of gene expression and biochemical parameters. The left kidneys were used for histopathological studies. RESULTS: The Cisplatin-induced nephrotoxicity was evident from the elevated levels of creatinine, urea, uric acid, and renal tissue MDA and also decreased levels of SOD, CAT, GPX, and GSH in renal tissue. Administration of Gallic acid significantly modulated nephrotoxicity markers, gene expression variations, and histopathological damage. CONCLUSION: Outcomes of the present investigation suggest that Gallic acid provides protection against CP-induced nephrotoxicity, but for application in people, further studies are needed.

Neonatal Hearing Screening: Prevalence of Unilateral and Bilateral Hearing Loss and Associated Risk Factors.

INTRODUCTION: Newborn hearing screening is essential for early identification of hearing loss to decrease the adverse effects of hearing loss. The objective of this study was to determine the prevalence of hearing loss and risk factors of congenital hearing loss in newborns. METHODS: In this analytical case-control study, a hearing screening test was performed for all newborns aged 3-14 days. RESULTS: Of 5,500 newborns evaluated, 24 newborns had hearing loss. The prevalence of hearing loss was 4.36 per 1,000. Of 24 hearing-impaired newborns, 15 had bilateral hearing loss (BHL) (62.5%) and nine had unilateral hearing loss (UHL) (37.5%). Among the neonates with hearing loss, the prevalence of hearing loss was higher (77.8%) in the right ear. The main risk factors identified in this study were low gestational age (P=0.001), hospitalization in the neonatal intensive care unit (NICU) (P=0.008), exposure to ototoxic drugs (P=0.001), gestational diabetes P=0.01), craniofacial anomalies (P=0.01), convulsion (P=0.03), consanguineous marriage of parents (P=0.001), low birth weight (P=0.01), and hyperbilirubinemia (P=0.001). CONCLUSION: The prevalence of hearing loss was higher in the right ear than in the left ear. NICU stay, use of ototoxic drugs, low gestational age (<35 weeks), gestational diabetes, craniofacial anomalies, convulsion, consanguineous marriage of parents, low birth weight, and hyperbilirubinemia were significant risk factors for congenital hearing loss in studied newborns.

Evaluating the protective effects of melatonin on di(2-ethylhexyl) phthalate-induced testicular injury in adult mice.

OBJECTIVE: Di (2-ethylhexyl) phthalate (DEHP) is a common phthalate derivative, interfering with normal function of reproductive system. The present study evaluated effects of melatonin on DEHP-induced testicular injury in mice. DESIGN: Thirty-two adult male mice were randomly divided to four groups; group I received normal saline, group II received DEHP, group III received DEHP and melatonin, and group IV was treated with melatonin alone. Body and testes weights, total antioxidant capacity (TAC), glutathione level and superoxide dismutase, glutathione peroxidase and catalase activities were measured. Serum testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and interleukin 1 beta (IL-1ß) and tumor necrosis factor (TNF-α) concentration were evaluated by ELISA assay. Also, malondialdehyde (MDA) and nitric oxide (NO) levels, sperm characteristics and histological changes of testes were analyzed. RESULTS: Body and testes weights were decreased in DEHP group. DEHP also reduced the number of spermatogonia, primary spermatocyte and sertoli cells as well as sperm vitality and progressive motility; these toxic effects were associated with alterations in serum hormone levels. Melatonin remarkably inhibited DEHP-induced reduction of body weight and antioxidant capacity. Melatonin reduced DEHP-induced elevation of NO, MDA, IL-1ß and TNF-α levels. Melatonin improved DEHP-induced changes in hormonal levels, number of sertoli cells, spermatogonia, and sperm viability and motility. CONCLUSION: Melatonin considerably inhibits DEHP-induced gonadotoxicity through reducing oxidative stress and inflammatory responses. These results suggest that melatonin may be considered as a promising agent to reduce toxic effects of endocrine disrupting chemicals such as DEHP on the male reproductive system.

A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia.

PURPOSE: Asthenozoospermia is a common cause of human male infertility characterized by reduced sperm motility. The molecular mechanism that impairs sperm motility is not fully understood. This study proposed to identify novel biomarkers by focusing on sperm tail proteomic analysis of asthenozoospermic patients. METHODS: Sperm were isolated from normozoospermic and asthenozoospermic semen samples. Tail fractions were obtained by sonication followed by Percoll gradient. The proteins were extracted by solubilization and subjected to two-dimensional gel electrophoresis (2-DE); then, the spots were analyzed using Image Master 2D Platinum software. The significantly increased/decreased amounts of proteins in the two groups were exploited by matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI-TOF-TOF) mass spectrometry. RESULTS: Three hundred ninety protein spots were detected in both groups. Twenty-one protein spots that had significantly altered amounts (p < 0.05) were excised and exploited using MALDI-TOF-TOF mass spectrometry. They led to the identification of the following 14 unique proteins: Tubulin beta 2B; glutathione S-transferase Mu 3; keratin, type II cytoskeletal 1; outer dense fiber protein 2; voltage-dependent anion-selective channel protein 2; A-kinase anchor protein 4; cytochrome c oxidase subunit 6B; sperm protein associated with the nucleus on the X chromosome B; phospholipid hydroperoxide glutathione peroxidase-mitochondrial; isoaspartyl peptidase/L-asparaginase; heat shock-related 70 kDa protein 2; stress-70 protein, mitochondrial; glyceraldehyde-3-phosphate dehydrogenase, testis-specific and clusterin. CONCLUSION: Fourteen proteins present in different amounts in asthenozoospermic sperm tail samples were identified, four of which are reported here for the first time. These proteins might be used as markers for the better diagnosis of sperm dysfunctions, targets for male contraceptive development, and to predict embryo quality.