Lipopolysaccharide In Male Rats Research Articles

The Antidiabetic Drug Metformin Attenuated Depressive and Anxietylike Behaviors and Oxidative Stress in the Brain in a Rodent Model of Inflammation Induced by Lipopolysaccharide in Male Rats.

Inflammation is considered to be a link between diabetes and central nervous system (CNS) disorders, including depression and anxiety. Metformin is suggested to have antioxidant, anti-inflammatory, and mood-improving effects. The aim of the current research was to investigate the effects of the antidiabetic drug metformin on depressive- and anxiety- like behaviors and oxidative stress in the brain in a rodent model of inflammation induced by lipopolysaccharide (LPS) in male rats. The rats were treated as follows: (1) Vehicle instead of metformin and lipopolysaccharide, (2) Lipopolysaccharide (1 mg/ kg) + vehicle instead of metformin, (3-5) Lipopolysaccharide + 50, 100, or 150 mg/ kg of metformin. After the behavioral tests, including open field (OF), elevated pulse maze (EPM), and force swimming (FS) tests, the brains were removed, and malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol, catalase (CAT) activity, interleukin-6 (IL-6) and superoxide dismutase (SOD) activity were determined. In the EPM, metformin increased the open arm time and entry and decreased closed arm time and entry. In the FS test, metformin lowered the immobility and increased active time compared to lipopolysaccharide. In the OF test, metformin increased total crossing and total distance, time spent, traveled distance, and crossing number in the central zone. As a result of metformin administration, IL-6, MDA, and NO metabolites were decreased while thiol content, SOD, and CAT activity were increased. The results indicated that the well-known antidiabetic drug metformin attenuated depressive- and anxiety-like behaviors induced by inflammation in rats. These beneficial effects are suggested to be due to their attenuating effects on neuroinflammation, oxidative stress, and NO in the brain.

Investigating the Effect of Luteolin on Interleukin-1β and Tumor Necrosis Factor-α in Inflammation Induced by Lipopolysaccharide in Male Rats

Background: Consumption of herbal flavonoids instead of chemical drugs has increased in the recent years due to fewer side effects as well as affordability. Objectives: In this study, the effect of luteolin was investigated on inflammation induced by lipopolysaccharide in male rat’s serum by measurement of the proinflammatory factors of IL-1β and TNF-α. Methods: Overall, 90 male Wistar rats weighing 180 to 200 grams were chosen and divided to control, Sham (solvent) and positive control (Dexamethasone 15 mg/kg. IP) groups, and also three experimental groups received doses of 5, 15, and 30 mg/kg of luteolin, intraperitoneally. Half an hour after injecting one of these compounds, lipopolysaccharide (30 μg/kg. IP) was injected. Then, at 4-, 12-, and 24-hour intervals, rats were anesthetized and blood samples were taken. Serum of samples were separated by centrifuging, and then, the samples were transferred to micro-tubes and were stored at -80°C. Measurement of interleukin (IL)-1β and tumor necrosis factor (TNF)-α was conducted by the enzyme linked immunosorbent assay (ELISA) method. Data were analyzed using the SPSS software, version 19. Results: Pre-injection with luteolin in 30 mg/kg dose caused a reduction in IL-1β at 4 (P < 0.05) and 24 hours (P < 0.01) after the LPS injection compared to the control group. Also, luteolin significantly decreased TNF-α level at 12 hours (5 and 30 mg/kg; P < 0.05, 0.01, respectively) and 24 hours (15 and 30 mg/kg; P < 0.05, 0.01, respectively) intervals after LPS injection. Furthermore, IL-1β and TNF-α were significantly decreased by dexamethasone injection at all three time intervals compared with the control. Conclusions: Luteolin caused a significant reduction in IL-1β and TNF-α of serum in acute inflammation induction. This impact is close to the dexamethasone effect as an anti-inflammatory steroid drug.

Effect of Interleukin 1β on the HPA Axis in H1-Receptor Knockout Mice

Objectives and Methods: Circulating cytokines such as interleukin-1 (IL-1), and tumor necrosis factor-alpha as well as lipopolysaccharide (LPS) are potent ACTH secretagogues, acting via stimulation of corticotropin-releasing hormone (CRH) and vasopressinergic neurons in the paraventricular nucleus of the hypothalamus (PVN). Histamine (HA) has been shown to stimulate ACTH secretion in rats, an effect in part mediated by CRH and arginine vasopressin (AVP). We have previously shown that inhibition of neuronal HA synthesis or central blockade of H₁ receptors (H₁R) decreased the ACTH response to LPS in male rats. To further elucidate the role of neuronal HA in cytokine-induced activation of the HPA axis, we compared the effect of H₁R knockout on IL-1β-induced ACTH secretion in adult male mice. Results: In H₁R knockout mice, ACTH secretion increased from basal levels of 261 to 492 pmol/l in response to IL-1β whereas the cytokine-induced ACTH secretion increased from 140 to 406 pmol/l in wild-type mice. Plasma corticosterone (CORT) rose from basal levels of 99 to 831 nmol/l in knockout mice upon IL-1β stimulation, whereas in wild-type mice CORT levels rose from 112 to 841 nmol/l. There was no significant difference in IL-1β-stimulated plasma ACTH or CORT levels between wild-type and knockout mice. Furthermore, there was no significant difference in basal or IL-1β-stimulated hypothalamic levels of histamine and tele-methyl-histamine between wild-type and knockout mice. HDC gene expression was significantly lower in knockout mice than in wild-type mice both under basal and IL-1β-stimulated conditions, while there were no significant differences in CRH gene expression in the PVN in knockout mice under basal and IL-1β-stimulated conditions. Increased basal expression of AVP in the PVN of knockout mice was observed in this study compared to wild-type mice. Conclusion: We conclude that the lack of the gene for histamine H₁R does not seem to be crucial for the ACTH and CORT response to IL-1β, either due to possible functional compensation in the H₁R knockout mouse or due to activation of pathways other than the neuronal histaminergic system.