Impact of Hydroxychloroquine on Fructose-induced Metabolic Syndrome in Rats: Promising Protective Effect

BACKGROUND: Hydroxychloroquine (HCQ) is used in the treatment of malaria and rheumatoid arthritis for a long time. Its effects on inflammation and immune modulation were noted. AIM: This study aims to investigate the effects of HCQ in fructose-induced metabolic syndrome and to explore its possible mechanisms. METHODS AND MATERIALS: Sixty male Sprague-Dawley rats were divided into Group I (negative control), Group II fed on high-fructose diet, and Group III fed on high fructose and subdivided into Group III-a (HCQ 50 mg/kg), Group III-b (HCQ 100 mg/kg), Group III-c (HCQ 200 mg/kg), and Group III-d (metformin 100 mg/kg). Body weight, blood glucose, liver enzymes, and lipid profile were measured. Insulin level, homeostatic model assessment (HOMA), soluble-intercellular adhesion molecule, and vascular cell adhesion molecule were assayed. Tumor necrosis factor (TNF)-α, adipokines (leptin, resistin, and adiponectin), and histological examination of pancreas were assessed. RESULTS: HCQ induces good effects on lipid profile and improves significantly HOMA, endothelial stress markers, and adiponectin, and reduces leptin and TNF-α levels. In addition, significant improvement in structural changes was noted in pancreas with different doses of HCQ. CONCLUSION: Favorable effects of HCQ in fructose-induced metabolic syndrome are promising and can be used early in those at risk of diabetes

Effect of combined gliclazide/metformin treatment on oxidative stress, lipid profile, and hepatorenal functions in type 2 diabetic patients

Background: Type 2 diabetes is a chronic condition that requires pharmacotherapy interventions. Metformin and gliclazide are widely used drugs in monotherapy. However, their complementary action made utilization of the combination of these drugs an appealing approach. Aims: The study compared major therapeutic potentials of combined metformin/gliclazide treatment over metformin monotherapy based on the following parameters: oxidative stress, lipid profile, and hepatorenal functions. Subjects and methods: This is a comparative study was conducted from March 2015 to March 2016. The study screened 80 type 2 diabetic patients, of which 40 patients underwent combined metformin + gliclazide therapy (500 mg BD + 80 mg OD, respectively). The other 40 were matched for age and duration of diabetes mellitus with the previous group and received metformin monotherapy (500 mg BD). The levels of fasting blood glucose (FBG), total glycated hemoglobin (HbA1c), lipid peroxidation, total antioxidant capacity, serum creatinine, aspartate and alanine transaminases, total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins were measured according to the standard methods. Results: Oxidative stress, lipid profile, and hepatorenal functions were comparable in patients of both groups. However, patients on metformin treatment showed significantly lower levels of FBG [7.61 (6.70–8.89) mmol/L vs. 9.00 (7.30–10.68) mmol/L; P = .022] and HBA1c [7.00 (6.40–7.65)% vs. 8.20 (7.20–9.75)%; P < .001] compared to those on combined therapy. Conclusion: Oxidative stress, lipids profile, and hepatorenal functions were not different in patients who were on combined metformin/gliclazide therapy and compared to those metformin alone. In contrast, glycemic control was poor in the diabetic patients undergoing combined therapy. Keywords: Diabetes mellitus, Gliclazide, Glucose, Lipids, Metformin, Oxidative stres

Neuroprotective Effect of Clobenpropit against Lipopolysaccharide-Induced Cognitive Deficits via Attenuating Neuroinflammation and Enhancing Mitochondrial Functions in Mice

Clobenpropit (CLO), an antagonist on histamine H3 receptors (HH3R), has been shown to protect NMDA-induced neuronal necrosis in cortical neuronal cell culture from rats. In this work, we explored its potential on lipopolysaccharide (LPS)-induced memory deficits, neuroinflammation, and mitochondrial dysfunction in mice. CLO (1 and 3 mg/kg, p.o.) was treated continually for 30 days, and neurotoxicity was induced by four doses of LPS (250 &micro;g/kg, i.p.). The radial arm maze (RAM) was used to access memory behaviors. After the REM test, brain tissue was collected from each mouse to estimate pro-inflammatory cytokines (TNF&alpha; and IL6), anti-inflammatory cytokines (TGF-&beta;1 and IL-10), cyclooxygenase-2 (COX 2), and mitochondrial respiratory chain complex (MRCC- I, II and IV) enzymes. CLO treatment reversed the LPS-induced behavioral deficits by a significant reduction in time taken to consume all five bites (TTB), working memory error (WME), and reference memory error (REM) in the REM test. Regarding neuroinflammation, it attenuated the release of COX, TNF-&alpha;, and IL-6, and augmented TGF-&beta;1 and IL-10 levels in the brain. Reversal of LPS-induced brain MRCC (I, II, and IV) levels also resulted with CLO treatment. From these findings, CLO promises neuroprotection against LPS-induced cognitive deficits by ameliorating neuroinflammation and restoring the MRCC enzymes in mice

Trimester pattern of change and reference ranges of hematological profile among Sudanese women with normal pregnancy

Trimester specific reference ranges of hematological indices were described in several populations; however, comparable reports among Sudanese women with normal pregnancy are lacking. To evaluate trimester pattern of change and reference ranges of hematological profile among Sudanese women with normal pregnancy, we followed 143 women with singleton gestation since early pregnancy until the third trimester in Saad Abu-Alela Hospital, Khartoum, Sudan, during the period of January-December 2015. Obstetrics and medical history was gathered using questionnaire and hematological profile was investigated using hemo-analyser. The first, second and third trimester mean (SD) [5th- 95th centile] of hematological profile were as follow: RBC counts 4.30 (0.36) [3.69- 4.93], 4.35 (0.36) [3.69-4.93], 4.08 (0.44) [3.44-4.78] ×106/mm3; hemoglobin concentration 10.81 (1.22) [8.92-12.74], 10.62 (0.93) [9.00-12.10], 10.83 (1.13) [8.82- 12.60] g/dL; hematocrit 35.38 (3.52) [30.12-40.30], 34.43 (2.51) [30.58-38.23], 35.17 (3.18) 29.66-40.04] %; WBC counts 7.69 (1.96) [4.36-11.20], 8.45 (1.97) [5.48- 12.13], 8.36 (2.11) [5.00-11.96] ×103/mm3; platelet counts 278.02 (66.93) [182.6- 418.0], 251.96 (64.17) [163.8-381.8], 238.36 (57.10) [150.4-346.2] ×103/mm3. The present study is the first to establish trimester specific, reference range for hematological profile among Sudanese women with normal pregnancy. The trimester reference range of RBC, WBC and platelets and other hematological indices are mostly parallel to international records

α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis

The clinical application of cyclosporine A (CsA) as an immunosuppressive agent is limited by its organ toxicity. We aimed to evaluate the effectiveness of α-lipoic acid against CsA-induced hepatotoxicity and to delineate the underlying molecular mechanisms. Male Wistar rats (n = 24, 8 per each group) received the vehicle, CsA (25 mg/kg) and/or ALA (100 mg/kg, p.o.) for 3 weeks. Biochemical markers of liver function (serum ALT, AST, ALP < GGT), oxidative stress (MDA, TAC, SOD, GSH, Nrf2/HO-1), inflammation (NF-κB, CD68, iNOS, NO, COX-2), and apoptosis (caspase-3) were assessed in serum and tissue. Liver histological analysis using H&E and Sirius red was performed. The development of liver injury in CsA-treated animals was indicated by elevated levels of liver enzymes, oxidants/antioxidants imbalance, inflammatory cells infiltration, up-regulated expression of inflammatory mediators, and apoptosis. These changes were associated with altered architecture of hepatic cells and fibrous connective tissue. ALA co-administration protected against CsA-induced liver damage and ameliorated biochemical changes and cellular injury. In conclusion, ALA demonstrated hepatoprotective potential against CsA-induced liver injury through combating oxidative stress, inflammation, and apoptosis, highlighting ALA as a valuable adjunct to CsA therapy

Thymoquinone, but Not Metformin, Protects against Gentamicin-Induced Nephrotoxicity and Renal Dysfunction in Rats

Background: Gentamicin (GM) is an antibiotic that is widely used to treat many Gram-negative bacteria, such as those involved in urinary tract infections. However, being nephrotoxic, GM dose adjustment and reno-protective elements must be concurrently administered with GM to minimize kidney damage. Oxidative stress plays a pivotal role in the pathogenesis of GM-induced nephrotoxicity. Thymoquinone (TQ) is a promising therapeutic substance, that is being extensively studied in many diseases, such as diabetes mellitus, cancer, hypertension, and others. The powerful antioxidant properties of TQ may greatly help in minimizing GM nephrotoxicity. Metformin (MF) is a well-known, clinically approved oral hypoglycaemic drug that has many other actions, including antioxidant properties. The aim of this work was to evaluate the possible antioxidant and reno-protective effects of TQ and metformin in GM-induced nephrotoxicity in the same model (rats) at the same time. In addition, we aimed to further understand the effects underlying GM-induced nephrotoxicity. Methods: Twenty male rats were randomly divided into four equal groups: the first group (control) received distilled water; the second group received GM only; the third group received concurrent oral TQ and GM; and the fourth group received concurrent oral MF and GM. After 4 weeks, renal function and histopathology, as well as levels of the oxidative markers glutathione peroxidase-1 (GLPX1), superoxide dismutase (SOD), and malondialdehyde (MDA) in the kidney tissues, were assessed. Results: Compared with the control group, and as expected, the GM-injected rats showed significant biochemical and histological changes denoting renal damage. Compared with GM-injected rats, the concurrent administration of TQ with GM significantly reduced the levels of serum creatinine, serum urea, and tissue MDA and significantly increased the levels of GLPX1 and SOD. Concurrent metformin administration with GM significantly increased the levels of both GLPX1 and SOD and significantly decreased the levels of tissue MDA but had no significant effect on serum creatinine and urea levels. Compared with GM-injected rats, the addition of either TQ or MF resulted in a reduction in endothelial proliferation and mesangial hypercellularity. Conclusions: Both TQ and MF effectively alleviated the oxidative stress in GM-induced nephrotoxicity in rats, with TQ but not MF producing a complete reno-protective effect. Further studies for evaluation of different reno-protective mechanisms of TQ should be conducted

Myristica fragrans Kernels Prevent Paracetamol-Induced Hepatotoxicity by Inducing Anti-Apoptotic Genes and Nrf2/HO-1 Pathway

Paracetamol is responsible for acute liver failure in humans and experimental animals when taken at high doses and transformed into a reactive metabolite by the liver cytochrome P450. On the other hand, nutmeg is rich with many phytochemical ingredients that are known for their ability to inhibit cytochrome P450. Hence, the present experiment was aimed at studying the hepatoprotective effect of Myristica fragrans (nutmeg), kernel extract (MFKE) in respect to paracetamol (acetaminophen; N-acetyl-p-amino-phenol (APAP))-induced hepatotoxicity in rats, focusing on its antioxidant, anti-inflammatory, and anti-apoptotic activities. Liver toxicity was induced in rats by a single oral administration of APAP (2 g/kg). To evaluate the hepatoprotective effect of MFKE against this APAP-induced hepatotoxicity, rats were pre-treated with either oral administration of MFKE at 300 mg/kg daily for seven days or silymarin at 50 mg/kg as a standard hepatoprotective agent. APAP intoxication caused a drastic elevation in liver function markers (transaminases, alkaline phosphatase, and total bilirubin), oxidative stress indicators (lipid peroxidation and nitric oxide), inflammatory biomarkers (tumour necrosis factor-&alpha;, interleukin-1&beta;, inducible nitric oxide synthase, and nuclear factor ĸB) and the pro-apoptotic BCL2 Associated X (Bax) and caspases-3 genes. Furthermore, analyses of rat liver tissue revealed that APAP significantly depleted glutathione and inhibited the activities of antioxidant enzymes in addition to downregulating two key anti-apoptotic genes: Cellular FLICE (FADD-like IL-1&beta;-converting enzyme)-inhibitory protein (c-FLIP) and B-cell lymphoma 2 (Bcl-2). Pre-treatment with MFKE, however, attenuated APAP-induced liver toxicity by reversing all of these toxicity biomarkers. This hepatoprotective effect of MFKE was further confirmed by improvement in histopathological findings. Interestingly, the hepatoprotective effect of MFKE was comparable to that offered by the reference hepatoprotector, silymarin. In conclusion, our results revealed that MFKE had antioxidant, anti-inflammatory, and anti-apoptotic properties, and it is suggested that this hepatoprotective effect could be linked to its ability to promote the nuclear factor erythroid 2&ndash;related factor 2 (Nrf2)/antioxidant responsive element (ARE) pathway