Liver dysfunction in sepsis is a major complication that amplifies multiple organ failure and increases the risk of death. Inflammation and oxidative stress are the main mediators in the pathophysiology of sepsis. Therefore, we investigated the role of menthol, a natural antioxidant, against sepsis-induced liver injury in female Wistar rats. Sepsis was induced by cecal ligation and puncture (CLP). Menthol (100 mg/kg) was given intragastric 2 h after CLP. Blood samples and liver tissues were collected 24 h after surgery. Menthol significantly (p < 0.05) attenuated the sepsis-induced elevation in serum liver enzymes and improved the hepatic histopathological changes. Menthol treatment significantly (p < 0.05) decreased hepatic levels of tumor necrosis factor-alpha, malondialdehyde, total nitrite, and cleaved caspase-3. It restored the hepatic levels of superoxide dismutase and reduced glutathione. Additionally, menthol significantly (p < 0.05) increased hepatic levels of B-cell lymphoma 2 (Bcl-2); an anti-apoptotic factor, and proliferating cell nuclear antigen (PCNA), a biomarker of regeneration and survival. Our results showed the therapeutic potential of menthol against liver injury induced by sepsis.
Despite being extremely potent against malignancies, cisplatin (CIS) has limited practical applicability due to its adverse effects such as testicular damage. Consequently, it becomes necessary to reduce its toxicity. In this study, cilostazol, a selective phosphodiesterase-3 inhibitor that is frequently used in the treatment of intermittent claudication, was examined for its ability to abrogate CIS-induces testicular toxicity and its ameliorative effect was compared with two phosphodiesterase inhibitors, tadalafil and pentoxifylline. The study also focused on the possible mechanisms involved in the proposed protective effect. Ten groups of rats were included; Group (1): control, Groups (2-4): 5 mg/kg tadalafil or 75 mg/kg pentoxifylline or 20 mg/kg cilostazol respectively), Group (5):7 mg/kg CIS, Group (6&7): CIS + 5 mg/kg tadalafil or 75 mg/kg pentoxifylline, Group (8-10) CIS+ 5, 10 or 20 mg/kg cilostazol respectively. CIS treated rats showed a significant decrease in testicular function, serum testosterone and reduced glutathione levels, and significant elevation in malondialdehyde, total nitrite levels, tumor necrosis factor-alpha and nuclear factor-kappa β alongside caspase-3. These outcomes were confirmed by marked testicular architecture deterioration. Contrary, Cilostazol in a dose-dependent manner showed potential protection against testicular toxicity, reversion of the disrupted testicular function and improvement of the histological alterations through rebalancing of oxidative stress, inflammatory and apoptotic biomarkers. In addition, cilostazol exerted more pronounced protective effect in comparison to tadalafil and pentoxifylline. In conclusion, administrations of cilostazol might ameliorate cisplatin-induced testicular impairment through alteration of oxidative stress, inflammation, and apoptotic pathway, offering a promising treatment for cisplatin -intoxication in the testes.
Introduction: Chronic kidney disease (CKD) carries a lot of co-morbidities. Urea rise may be related to decline in glomerular filtration rate, under nutrition or hyper catabolic state. According to urea percentile curves (UPC), patients with a given glomerular filtration rate show wide range of urea levels. Correlation between urea percentiles and CKD patients' co-morbidities was suggested in many studies since Montini 2003.Aim of the study: to evaluate the value of UPCs as a simple tool in monitoring metabolic status and progress of CKD comorbidities. Methods: Retrospective revision of patients' files for their urea levels and GFR at the time of diagnosis and long period after (follow-up). Accordingly, each patient was plotted on UPC graph to determine his urea percentile (UP) at each setting. Patients were classified according to their urea percentile as low, moderate and high UP groups, and classified according to urea percentile progress pattern as ascending, descending and stable groups. Correlations between their co-morbidities and their urea percentiles were statistically analysed. Results: showed correlation between morbidity markers changes in relation to progress course of UP with significant differences in the values of phosphorus rise, bicarbonate changes and frequency of hyperphosphatemia between the 3 groups of urea percentile progress pattern. Conclusion: Follow up pattern of urea percentile in these children is a simple and helpful tool in monitoring their co-morbidities.
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