gossypin and Inflammation

Acute Lung Injury (ALI) is a critical medical condition that induces the injury into the lung tissue, resulting in decreased the oxygen levels in the circulation and finally causes the respiratory failure. In this study, we try to made effort for scrutinized the preventive effect of gossypin against lipopolysaccharide (LPS) induced lung inflammation and explore the underlying mechanism. LPS (7.5 mg/kg) was used for induction the lung inflammation in the rats and rats were received the oral administration of gossypin (5, 10 and 15 mg/kg). The wet to dry weight lung ratio and lung index were estimated. The bronchoalveolar lavage fluid (BALF) were collected to determination the inflammatory cells, total protein, macrophages and neutrophils. ELISA kits were used for the estimation of antioxidant, inflammatory cytokines, inflammatory parameters, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) parameters. Finally, we used the lung tissue for scrutinize the alteration in the lung histopathology. Gossypin treatment significantly (p < .001) reduced the W/D ratio of lung tissue and lung index. Gossypin significantly (p < .001) decreased the total cells, neutrophils, macrophages and total protein in BALF. It is also altered the level of inflammatory cytokines, antioxidant and inflammatory parameters, respectively. Gossypin improved the level of Nrf2 and HO-1 at dose dependent manner. Gossypin treatment remarkably enhance the ALI severity via balancing the structural integrity of lung tissue, decrease the thickness of the alveolar wall, decline the pulmonary interstitial edema, and number of inflammatory cells in the lung tissue. Gossypin is a promising agent for the treatment of LPS induced lung inflammation via altering Nrf2/HO-1 and NF-κB.

Topics: Acute Lung Injury; Animals; Antioxidants; Cytokines; Heme Oxygenase-1; Inflammation; Lipopolysaccharides; Lung; NF-E2-Related Factor 2; NF-kappa B; Pneumonia; Rats; Signal Transduction

Sepsis is a complex pathophysiological event involving systemic inflammatory response syndrome, multiple organ dysfunction syndrome and tissue damage such as acute lung injury (ALI). Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Antioxidant, antibacterial and antiinflammatory effects of gossypin (GOS)-like flavonoids have been shown and we have hypothesized that GOS have roles in sepsis induced inflammation of lungs.. Cecal ligation and puncture (CLP) induced sepsis model was induced in rats. Effects of GOS on oxidative stress, histopathology, nuclear factor kappa B (NF-κB), IL-6 positivity and NLRP3, HMGβ1, TNF-α, NF-κB, IL-1β mRNA expression levels were evaluated in lung tissues of the septic rats.. GOS 20 (20 mg/kg) administration to septic rats decreased oxidative stress and supported antioxidant system in lungs. GOS administration also decreased the tissue NF-κB and IL-6 immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. HMGβ1, NLRP3, NF-κB, IL-1β, and TNF-α mRNA expression significantly increased in the CLP group. Both doses of GOS significantly reduced these mRNA expression as compared with the levels in the CLP group demonstrating its anti-inflammatory potential.. GOS administration, may represent a novel treatment for the prevention of lung damage occurred after sepsis induction. This effect of GOS might be related to its anti-inflammatory potential that result in decreased cytokine response and improved oxidative status.

Topics: Acute Lung Injury; Animals; Antioxidants; Cytokines; Disease Models, Animal; Female; Flavonoids; HMGB Proteins; Inflammation; Interleukin-1beta; Interleukin-6; Lung; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Rats; Rats, Wistar; Sepsis; Tumor Necrosis Factor-alpha

A group of flavonoids isolated from medicinal plants and which are selective inhibitors of lipoxygenase activity in vitro: sideritoflavone, cirsiliol, hypolaetin-8-O-beta-D-glucoside, hypolaetin, oroxindin, quercetagetin-7-O-beta-D-glucoside, gossypin, hibifolin and gossypetin, besides leucocyanidol, have been studied for their effects on acute responses induced by carrageenin in mice. The oral administration of flavonoids to mice inhibited dose-dependently the development of paw oedema at 1, 3 and 5 h after carrageenin injection. A similar administration of flavonoids induced a dose-dependent inhibition of leukocyte accumulation in inflammatory exudates following intraperitoneal injection of carrageenin into mice. Some of the flavonoids exhibited a potency against leukocyte infiltration similar to that seen for inhibition of carrageenin oedema at 3 h of induction. In agreement with data reported in rats, indomethacin was much more effective on inhibition of prostaglandin E2 (PGE2) formation than on leukocyte infiltration in mice. The selectivity of flavonoids towards lipoxygenase is not retained in vivo since they behave as dual inhibitors of PGE2 and leukotriene B4 (LTB4) formation in peritoneal exudates. Our data support the inhibition of arachidonic acid metabolism as one of the mechanisms by which flavonoids exert their anti-inflammatory effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arachidonic Acids; Carrageenan; Dinoprostone; Edema; Flavonoids; Inflammation; Leukocytes; Leukotriene B4; Male; Mice; Peritonitis; Plants, Medicinal