Impact of Human Umbilical Cord Blood Mononuclear Cells on Gentamicin-Induced Renal Injury and Genotoxicity in Rats.

Background: Acute kidney injury (AKI), also known as acute renal failure (ARF), has received considerable critical attention in recent years. Gentamicin (GM) is an antibiotic whose prolonged use results in AKI with a high mortality rate. Methods: Fifty adult female albino rats weighing 150-200 g were used. The animals were divided into five groups: the first group was the normal healthy control one, the second group received only 1 × 106 HUCB mononuclear cells (MNCs)/rat by intravenous (iv) injection, the third diseased group was given GM 100 mg/kg for 10 consecutive days by intraperitoneal injections, the fourth preventive group received 1 × 106 HUCB MNCs/rat by iv injection 24 h before gentamicin treatment, and the fifth treated group received 1 × 106 HUCB MNCs/rat by iv injection 24 h after gentamicin treatment. After 1 week of treatment, blood samples were collected, and kidneys were removed for histopathological examination. Results: Rats treated with HUCB MNCs in the treated group had a significant decrease in renal damage, low levels of biomarkers for nephrotoxicities such as serum creatinine and blood urea nitrogen, and low chromosomal aberrations compared to the diseased third group. The gene expression of KIM-1 and NGAL was decreased in response to HUCB treatment. Conclusions: HUCB MNCs have a curative effect against AKI and gentamicin-induced genotoxicity owing to their regenerative property.

Antioxidant and Anti-Inflammatory Effects of Crocin Ameliorate Doxorubicin-Induced Nephrotoxicity in Rats.

Doxorubicin is a drug that belongs to the anthracycline antibiotics. Nephrotoxicity is one of the serious side effects of doxorubicin treatment. Crocin, which is one of the most bioactive components of saffron, has antioxidant, anti-inflammatory, and antitumor effects. The current study was aimed at investigating the possible protective effects of crocin against doxorubicin-induced nephrotoxicity to elucidate the underlying mechanism of this effect. The study included four groups, six rats in each group: normal control, crocin control, doxorubicin, and crocin/doxorubicin. Doxorubicin and crocin/doxorubicin groups received intraperitoneal injections of doxorubicin (3.5 mg/kg twice weekly for 3 weeks). Rats in the crocin control group and the crocin/doxorubicin group were treated with intraperitoneal injections of crocin (100 mg/kg body weight per day) for 3 weeks. Biomarkers of kidney function and oxidative stress as well as the abundance of mRNA for nuclear factor-κß and inducible nitric oxide synthase were evaluated. In addition, the abundance of cyclooxygenase 2 and tumor necrosis factor α immunoreactivity was evaluated. Crocin treatment had renoprotective effects manifested by significant improvement in kidney function as well as a reduction in the abundance of biomarkers of oxidative stress markers and inflammatory mediators. In conclusion, crocin has a protective effect against doxorubicin-induced nephrotoxicity in rats by serving as an antioxidant and attenuating the expression of NF-κB, iNOS, COX2, and TNFα.

Modulation of the IL-23/IL-17 axis by fenofibrate ameliorates the ovalbumin/lipopolysaccharide-induced airway inflammation and bronchial asthma in rats.

The overlapping between asthmatic subtypes, including both CD4+ T helper (TH)2 and TH17 cells, is found in the natural course of allergic asthma, especially in exacerbations and severe and insensitive forms to steroids, which are in need of new molecular therapies. In the TH2-subset mediated asthma, fenofibrate displays therapeutic promises, besides evidenced therapeutic effects on TH17-mediated colitis and myocarditis. Therefore, the effects of fenofibrate versus dexamethasone on IL-23/IL-17 axis in ovalbumin (OVA)/lipopolysaccharide (LPS)-induced airway inflammation and bronchial asthma in rats were explored. The OVA/LPS sensitization and challenge were performed for 28 days in male Wistar rats. After sensitization, fenofibrate (100 mg/kg/day) or dexamethasone (2.5 mg/kg/day) was orally administered from the day 15 to 28. Either fenofibrate or dexamethasone attenuated the severity of OVA/LPS-induced airway inflammation and bronchial asthma through significant ameliorations in the total serum immunoglobulin (Ig)E assay; the total and differential leukocytic counts in the bronchoalveolar lavage (BAL) fluid; the lung inflammatory cytokines such as interleukin (IL)-4, IL-13, IL-17, and IL-23, transforming growth factor (TGF)-ß1, and tumor necrosis factor(TNF)-α levels; and the lung IL-17 and IL-23 expressions. In addition to the reduction in the inflammatory and fibrotic histopathological scores, fenofibrate significantly ameliorated the BAL neutrophilic count and the lung IL-17 and IL-23 expressions in comparison to dexamethasone. The suppression of IL-23/IL-17 axis could be considered a molecular therapeutic target for fenofibrate in OVA/LPS-induced airway inflammation and bronchial asthma. Combined therapeutic regimens of fenofibrate and steroids should be furtherly investigated in severe and resistant asthma.

Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: effects on hepatic peroxisome proliferator-activated receptor-gamma receptors.

Targeting peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-γ modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg·kg-1·day-1) or NTZ (200 mg·kg-1·day-1) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-γ protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-γ protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-γ receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.

Effect of feeding a high-fat diet independently of caloric intake on reproductive function in diet-induced obese female rats.

INTRODUCTION: Globally, the prevalence of overweight and obesity is increasing, predisposing females to health hazards including compromised reproductive capacity. Our objective was to investigate the effect of ad libitum, isocalorically and hypocalorically restricted high-fat diet (HFD) feeding on reproductive function in diet-induced obese female rats. MATERIAL AND METHODS: Twenty female albino Sprague Dawley rats were used; 5 rats were kept on a standard pellet animal diet to serve as a control group (A) and 15 rats were fed a HFD for 9 weeks to induce obesity. The HFD fed animals were equally divided into three groups: an ad libitum HFD group (B), an isocalorically restricted HFD group (C), and a hypocalorically restricted HFD group (D). Estrous cyclicity, hormonal levels, ovarian histopathology and caspase-3 immunoreactivity were evaluated. RESULTS: The HFD-fed rats in groups B, C and D had significant irregularity in estrous cyclicity Vs group A (p = 0.001, 0.003 and 0.034 respectively). Groups C and D had significant reduction in serum progesterone level (p = 0.006 and 0.018 Vs A). Isocaloric restriction of HFD feeding significantly increased serum LH. Groups B and C had a significant increase in caspase-3 expression in the ovary (p < 0.001). CONCLUSIONS: Ad libitum HFD interfered with the normal estrous cycle and enhanced apoptosis of luteal cells in obese female rats. The HFD restriction interfered with the normal estrous cycle and caused functional insufficiency of the corpus luteum in obese female rats. These results suggest that HFD feeding determinately affects female reproductive function independently of caloric intake.