Effects of unpredictable chronic mild stress on the cellular redox state and mitochondrial energy homeostasis in rat adipose tissue: A comprehensive metabolic study.

Unpredictable chronic mild stress (UCMS) leads to variable metabolic effects. Oxidative stress (OS) of adipose tissue (AT) and mitochondrial energy homeostasis is little investigated. This work studied the effects of UCMS on OS and the antioxidant/redox status in AT and mitochondrial energy homeostasis in rats. Twenty-four male Wistar rats (180-220 g) were divided into two equal groups; the normal control (NC) group and the UCMS group which were exposed to various stresses for 28 days. An indirect calorimetry machine was used to measure volumes of respiratory gases (VO2 & VCO2 ), total energy expenditure (TEE), and food intake (FI). The AT depots were collected, weighed, and used for measuring activities and gene expression of key antioxidant enzymes (GPx1, SOD, CAT, GR, GCL, and GS), OS marker levels including superoxide anion (SA), peroxynitrite radical (PON), nitric oxide (NO), hydrogen peroxide (H2 O2 ), lipid peroxides (LPO), t-protein carbonyl content (PCC), and reduced/oxidized glutathione levels (GSH, GSSG). Additionally, AT mitochondrial fractions were used to determine the activities of the tricarboxylic acid cycle (TCA) cycle enzymes (CS, α-KGDH, ICDH, SDH, MDH), respiratory chain complexes I-III, II-III, IV, the nicotinamide coenzymes NAD+ , NADH, and ATP/ADP levels. Compared with the NC group, the UCMS group showed very significantly increased OS marker levels, lowered antioxidant enzyme activities and gene expression, as well as lowered TCA cycle and respiratory chain activity and NAD+ , NADH, and ATP levels (p < .001 for all comparisons). Besides, the UCMS group had lowered TEE and insignificant FI and weight gain. In conclusion, AT of the UCMS-subjected rats showed a state of disturbed redox balance linked to disrupted energy homeostasis producing augmentation of AT.

The molecular mechanisms of lithium-induced cardiotoxicity in male rats and its amelioration by N-acetyl cysteine.

Lithium is one of the most powerful and commonly used medications for the treatment of various psychiatric diseases, especially bipolar disorder. However, it has a narrow therapeutic index with toxic effects on various organs. There are several case reports of lithium-induced arrhythmia and ischemia. The current work aimed to study the toxic effects of lithium on the heart of adult albino rats and its molecular mechanisms and the ameliorating effect of N-acetyl cysteine (NAC). Sixty adult male Wistar albino rats were classified into four groups; control, NAC-treated received NAC 500 mg/kg/week dissolved in 1 ml 0.9% sodium chloride intraperitoneal, lithium-treated received 52.5 mg/kg/day of lithium carbonate dissolved in 1 ml 0.9% sodium chloride orally by gavage, and lithium-and-NAC-treated (group IV) received lithium and NAC in the previous doses. After 12 weeks, the rats of group III showed a significant accumulation of ascites and a decrease in the mean arterial blood pressure and electrocardiographic (ECG) findings of ischemia and arrhythmia. In addition, there was an elevation in cardiac biomarkers creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and several histological lesions with a significant increase in the area % of Van Gieson, endothelial nitric oxide synthase (eNOS), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreaction. There was significant upregulation of microRNA-1, microRNA-21 (miRNA-21), and microRNA-29 (miRNA-29). MiRNA-21 was strongly positively correlated to the area % of 8-OHdG, while miRNA-29 was strongly positively correlated to the area % of Van Gieson staining. NAC significantly improved the cardiotoxic effects of lithium. Being a nontoxic and safe antioxidant, NAC can be used to ameliorate lithium-induced cardiac injury.

Ameliorative effect of combined low dose of Pioglitazone and omega-3 on spermatogenesis and steroidogenesis in diabetic rats.

BACKGROUND: Chronic hyperglycemia is linked to either subfertility or infertility among diabetic males. Pioglitazone is one of the thiazolidinediones (TZDs) drugs that are selective peroxisome proliferator-activated receptor (PPAR-γ agonists used for treating type 2 diabetes mellitus (T2DM). AIM: This study aims to explore the possible effect of low Pioglitazone dose and omega (ω-3) on rat male reproductive function. Furthermore, we evaluated the add-on effect of combined use of low Pioglitazone dose of and ω-3 on reproductive functions in adult male T2DM rats. METHODS: Fifty adult male rats were included and subdivided into control and four test subgroups. T2DM was induced in test groups and subdivided into non-treated T2DM, ω-3 treated, 0.6 mg/kg Pioglitazone treated, and combined treated group (orally by gavage). Following 16 weeks, final body weight, testicular weight, fasting plasma glucose, and serum testosterone levels were measured. Semen analysis, testicular testosterone, malondialdehyde (MDA) concentrations, superoxide dismutase (SOD) activity, immunohistochemistry staining for apoptosis marker B-cell lymphoma protein 2 (Bcl-2), proliferation marker as proliferating cell nuclear antigen (PCNA), estrogen receptor α (ERα), androgen receptor (AR) were determined. Caspase-3, nuclear factor-kappa B (NF-kB), glucose transporter 3 (GLUT3), 17ß-hydroxysteroid dehydrogenases (17ß-HSD) PPARγ, and PPARα genes expression were analyzed by real-time polymerase chain reaction (RT-PCR). RESULTS: Our findings revealed that treatment with low dose of Pioglitazone or ω-3 significantly lowered fasting plasma glucose and MDA levels, ameliorated diabetes effects on histological damage, improved antioxidant activity (SOD), significantly improved anti-apoptosis BCL-2 and proliferation (PCNA), remarkably elevated ERα, AR, 17ß-HSD PPARγ, and PPARα expression with significant reduction in caspase-3, NF-kB genes expression and improved semen quality as well. Combined use of low dose of and ω-3 has better effects on all measured parameters. CONCLUSION: Small Pioglitazone dose and ω-3 possess beneficial effects on spermatogenic and steroidogenic functions in adult diabetic rat; while combined use of both has an add-on effect.