The protective effect of pregabalin and xanthenone on testicular ischemia/reperfusion injury in rats.

BACKGROUND: Torsion of the spermatic cord is a hazardous and common urologic issue. The current work evaluates the possible protective effect of pregabalin (PGB) and xanthenone (XAN) in testicular ischemia/reperfusion injury induced by testicular torsion/detorsion in rats. MATERIALS AND METHODS: Seven groups of adult male Wistar albino rats were allocated randomly into seven groups, namely, sham control, torsion/detorsion (T/D), PGB 50 mg/kg, PGB 100 mg/kg, XAN 1 mg/kg, XAN 2 mg/kg, and PGB 50 mg/kg plus XAN 1 mg/kg groups. Serum cholesterol and testosterone levels were determined. Also, the levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-қB), angiotensin (Ang) II, Ang-(1-7), and angiotensin-converting enzyme2 (ACE2) were assessed in testicular tissue. Immunohistochemical analysis of heme oxygenase-1 (HO-1) and caspase-3 was performed. Finally, the histopathological examination of the testicular tissues was performed. RESULTS: The PGB 50 mg/kg, PGB 100 mg/kg, XAN 1 mg/kg, XAN 2 mg/kg, and PGB 50 mg/kg plus XAN 1 mg/kg groups showed a significant decrease in serum cholesterol, MDA, NO, TNF-α, NF-қB, and Ang-II levels coupled with a significant increase in both testosterone and ACE2 expression. Furthermore, all test groups showed a significant improvement in the histopathological picture with a reduction in caspase-3 and an increase in HO-1 immunoexpression in testicular tissue. CONCLUSION: PGB and XAN may have promising effects on preventing testicular T/D injury through antioxidant, anti-inflammatory, and antiapoptotic actions.

Clinicopathological characteristics and predictors of outcome of rapidly progressive glomerulonephritis: a retrospective study.

BACKGROUND: Globally, there are regional and time-based variations in the prevalence, etiology, and prognosis of rapidly progressive glomerulonephritis (RPGN). Prognosis of RPGN is poor, with a higher risk of death and end stage renal disease (ESRD) even with immunosuppressive medications. In the Middle East and North Africa, the studies on this disease are very limited. Therefore, we determined the predictors of outcome of RPGN. METHODS: We retrospectively assessed 101 adult patients over age of 18, diagnosed with RPGN based on renal biopsy illustrating crescents in ≥ 50% of the glomeruli. Patients who had crescents in their renal biopsies that were < 50% and those who refused to consent to a renal biopsy were excluded. We categorized the patients into 3 groups based on immunohistochemistry; type I, type II and type III. Then, depending on renal loss, we divided them into ESRD and non-ESRD groups. The clinical history and physical examination were retrieved. Additionally, 24-hour urine protein, urine analysis, renal function tests, serum albumin, complete blood count, antinuclear antibodies, anti-double stranded DNA antibodies, ANCA antibodies and serum complement levels were checked. Each patient underwent a kidney biopsy for immunohistochemistry and light microscopy. The percentage of crescentic glomeruli, number of sclerosed glomeruli, tertiary lymphoid organ (TLO), neutrophil infiltration, endocapillary or mesangial hypercellularity, interstitial fibrosis with tubular atrophy (IFTA) were analyzed. Primary outcomes (remission, ESRD and mortality) and secondary outcomes were assessed. RESULTS: Type II was the most frequent cause of RPGN (47.5%), followed by type III (32.7%) and type I (19.8%). 32 patients (31.7%) died during follow up, whereas 60 patients (59.4%) developed ESRD. In 41 patients (40.6%), remission occurred. Oliguria, serum creatinine, and need for HD at presentation were significantly increased in ESRD group compared to non-ESRD group (P < 0.001 for each). Mesangial proliferation, IFTA, TLO formation, sclerotic glomeruli and fibrous crescents were also significantly increased in ESRD group in comparison to non-ESRD group (P < 0.001 for each). Glomerulosclerosis (P = 0.036), and IFTA (P = 0.008) were predictors of ESRD. Infections (P = 0.02), respiratory failure (P < 0.001), and heart failure (P = 0.004) were mortality risk factors. CONCLUSION: Type II RPGN was the most common. Infection was the most frequent secondary outcome. Oliguria, glomerulosclerosis, the requirement for hemodialysis at presentation, IFTA and TLO formation were predictors of ESRD. Respiratory failure, heart failure and infections were significant predictors of mortality.

Aprepitant boasted a protective effect against olanzapine-induced metabolic syndrome and its subsequent hepatic, renal, and ovarian dysfunction; Role of IGF1/p-AKT/FOXO1 and NFκB/IL-1ß/TNF-α signaling pathways in female Wistar albino rats.

Olanzapine-induced metabolic syndrome (MS) is a primary risk factor for insulin resistance, hepatorenal damage, and polycystic ovarian syndrome. The objective of the current study was to assess the protective effects of aprepitant (AP) against MS caused by olanzapine and the associated ovarian, renal, and liver dysfunction via modulation of IGF1/p-AKT/FOXO1 and NFκB/IL-1ß/TNF-α signaling pathways. AP mitigated all biochemical and histopathological abnormalities induced by olanzapine and resulted in a significant reduction of serum HOMA-IR, lipid profile parameters, and a substantial decrease in hepatic, renal, and ovarian MDA, IL-6, IL-1ß, TNF-α, NFκB, and caspase 3. Serum AST, ALT, urea, creatinine, FSH, LH, and testosterone also decreased significantly by AP administration. The FOXO 1 signaling pathway was downregulated in the AP-treated group, while GSH, SOD, and HDL cholesterol levels were elevated.