ABSTRACT
The clinical usefulness of doxorubicin (DOX) is limited by its serious adverse effects, such as cardiotoxicity. Pregnenolone demonstrated both anti-inflammatory and antioxidant activity in animal models. The current study aimed to investigate the cardioprotective potential of pregnenolone against DOX-induced cardiotoxicity. After acclimatization, male Wistar rats were randomly grouped into four groups: control (vehicle-treated), pregnenolone (35 mg/kg/d, p.o.), DOX (15 mg/kg, i.p, once), and pregnenolone + DOX. All treatments continued for seven consecutive days except DOX, which was administered once on day 5. The heart and serum samples were harvested one day after the last treatment for further assays. Pregnenolone ameliorated the DOX-induced increase in markers of cardiotoxicity, namely, histopathological changes and elevated serum levels of creatine kinase-MB and lactate dehydrogenase. Moreover, pregnenolone prevented DOX-induced oxidative changes (significantly lowered cardiac malondialdehyde, total nitrite/nitrate, and NADPH oxidase 1, and elevated reduced glutathione), tissue remodeling (significantly decreased matrix metalloproteinase 2), inflammation (significantly decreased tumor necrosis factor-α and interleukin 6), and proapoptotic changes (significantly lowered cleaved caspase-3). In conclusion, these findings show the cardioprotective effects of pregnenolone in DOX-treated rats. The cardioprotection achieved by pregnenolone treatment can be attributed to its antioxidant, anti-inflammatory, and antiapoptotic actions.
ABSTRACT
Objectives: Acute Kidney Injury (AKI) is characterized by a rapid and reversible decline in renal function with a rapid decrease in Glomerular Filtration Rate (GFR), which is associated with high mortality. Rhabdomyolysis accounts for 10-40% of AKI, to which the therapeutic approach is limited. Klotho is a protein that modulates sodium-phosphate co-transporters, ion channels that have been reported to have a renal protective effect. Guanosine, a purine nucleoside, has already been reported to have a renal protective effect; however, the mechanism of such protection and its relation to Klotho modification has not been evaluated yet. This study aims to evaluate the mechanism of the protective effect of guanosine against rhabdomyolysis-induced AKI and its relation to the expression of the Klotho gene. Materials and Methods: In the current study, rats were divided into three groups: control, glycerol-induced AKI, and guanosine-treated. Serum urea and creatinine levels, renal tissue Total Antioxidant Capacity (TAC), and Klotho and Cystatin C genes expression were evaluated. Furthermore, caspase-3 immunostaining and histopathological evaluations were done. Results: Results showed that guanosine treatment resulted in a significant reduction in serum urea and creatinine, Cystatin C genes expression, and caspase-3 immunoexpression, and an increase in TAC and Klotho genes expression. Results also revealed an improvement of renal histopathology when compared with the glycerol-induced AKI group. Conclusion: Guanosine may be a promising agent in the treatment of rhabdomyolysis-induced AKI. The proposed mechanism for guanosine may be through its ability to enhance Klotho gene expression in renal tissue, with subsequent antioxidant and anti-apoptotic activity.
ABSTRACT
OBJECTIVE: To evaluate the female sexual dysfunction in both type 1 and type 2 diabetes mellitus (DM). METHODS: This cross-sectional study was carried out at Suez Canal University Hospitals from the start of February 2015 to the end of May 2016 among 189 married premenopausal women attending endocrinology and diabetology outpatient clinic for regular follow-up; 25 of whom refused to participate and 18 more were excluded due to incomplete data sets resulting in a final sample of 146 diabetic females. Ninety healthy women were recruited from the administrative staff at the hospital as a control group. Sexual dysfunction was assessed using female sexual function index (FSFI), a validated 19-item, self-administered, screening questionnaire comprising the six major sexual domains: desire, arousal, lubrication, orgasm, satisfaction and pain. Responses to each question were reported and scored on 0-5 scale with 0 representing no sexual activity and 5 suggestive of normal sexual activity. RESULTS: Prevalence of sexual dysfunction was significantly higher in both type 1 and 2 DM groups (44 and 25%, respectively) than in the control group (9%). FSFI mean total score was significantly lower in type 1 DM (21.1 ± 3.9) than type 2 DM (26.4 ± 4.2) and both were significantly lower than the control group (31.5 ± 5.8). With regard to FSFI domains, mean values for desire, arousal, lubrication, orgasm, satisfaction and pain were significantly lower in both type 1 and type 2 DM groups when compared with the controls. CONCLUSION: FSD is a significant health problem among premenopausal diabetic Egyptian women. Type 1 DM women were more affected than type 2 DM that in turn was more affected than healthy control females.
