Exploring redox imbalance and inflammation for asthma therapy.

BACKGROUND: Asthma is a prolonged inflammatory disorder of the airways, that affects an estimated 300 million people worldwide. Asthma is triggered by numerous endogenous and exogenous stimuli with symptoms like wheezing, cough, short of breath, chest tightening, airway obstruction, and hyperreactivity observed in patients. OBJECTIVE: The review seeks to identify targets of redox imbalance and inflammation that could be explored to create effective treatments for asthma. METHODS: The methodology involved a search and review of literature relating to asthma pathogenesis, redox homeostasis, and inflammation. RESULTS:  Eosinophils and neutrophils are involved in asthma pathogenesis. These inflammatory cells generate high levels of endogenous oxidants such as hydrogen peroxide and superoxide, which could result in redox imbalance in the airways of asthmatics. Redox imbalance occurs when the antioxidant systems becomes overwhelmed resulting in oxidative stress. Oxidative stress and inflammation have been linked with asthma inflammation and severity. Reactive oxygen species (ROS)/reactive nitrogen species (RNS) cause lung inflammation by activating nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), activator protein-1, as well as additional transcription factors. These factors stimulate cytokine production which ultimately activates inflammatory cells in the bronchi, causing lung cellular injury and destruction. ROS/RNS is also produced by these inflammatory cells to eradicate invading bacteria. Antioxidant treatments for asthma have not yet been fully explored. CONCLUSION: Redox and inflammatory processes are viable targets that could be explored to create better therapy for asthma.

Inhibition of Kupffer cell functions modulates arsenic intoxication in Wistar rats.

Study determined the influence of the inhibition of Kupffer cell functions by GdCl3 in arsenic intoxication. Twenty-four Wistar rats weighing between 150 and 160 g were randomly assigned into four groups. Group 1 received sodium arsenite (1.5 mg/kg b.w.) once a day, Group 2 received GdCl3 (2 mg/kg b.w.) once, 24 hours before commencing the arsenite (1.5 mg/kg b.w.) treatment. Group 3 received GdCl3 (2 mg/kg b.w.) once and subsequently given distilled water. Group 4 received distilled water only. The treatments were daily by oral gavage and lasted for 28 days. Animals were euthanized 24 hours after the last treatment. Arsenic exposure elevated the activities of rat plasma AST, ALT, ALP and γ-GT, indicative of liver injury. Arsenic exposure in rat lowered GSH concentration but potentiated inflammation and oxidative stress evidenced in the raised levels of MPO, NO and MDA. Rats with arsenic exposure were predisposed to atherosclerosis, lowering the HDL-C but elevated the LDL-C concentration. The histopathological assessment showed degenerating cellular lesion caused by arsenic. However, the inhibition of Kupffer cell functions by GdCl3 suppressed arsenic intoxication improving the liver function indices, oxidative stress status, lipid profile, neutrophilic inflammation and ultimately restored the cellular architecture. Data suggest that specific inhibition of Kupffer cells by GdCl3 protected against arsenic intoxication.

Antidiarrhoeal Activity of Musa paradisiaca Sap in Wistar Rats.

The folkloric claim of Musa paradisiaca sap in the management of diarrhoea is yet to be substantiated or refuted with scientific data. Therefore, the aim of the current study was to screen the sap of M. paradisiaca for both its secondary metabolites and antidiarrhoeal activity at 0.25, 0.50, and 1.00 mL in rats. Secondary metabolites were screened using standard methods while the antidiarrhoeal activity was done by adopting the castor oil-induced diarrhoeal, castor oil-induced enteropooling, and gastrointestinal motility models. The sap contained flavonoids, phenolics, saponins, alkaloids, tannins, and steroids while cardiac glycosides, anthraquinones, triterpenes, cardenolides, and dienolides were not detected. In the castor oil-induced diarrhoeal model, the sap significantly (P < 0.05) prolonged the onset time of diarrhoea, decreased the number, fresh weight, and water content of feaces, and increased the inhibition of defecations. Na(+)-K(+)-ATPase activity in the small intestine increased significantly whereas nitric oxide content decreased. The decreases in the masses and volumes of intestinal fluid by the sap were accompanied by increase in inhibition of intestinal fluid content in the enteropooling model. The sap decreased the charcoal meal transit in the gastrointestinal motility model. In all the models, the 1.00 mL of the sap produced changes that compared well with the reference drugs. Overall, the antidiarrhoeal activity of Musa paradisiaca sap attributed to the presence of alkaloids, phenolics, flavonoids, and/or saponins which may involve, among others, enhancing fluid and electrolyte absorption through de novo synthesis of the sodium potassium ATPase and/or reduced nitric oxide levels.

Antioxidant and drug detoxification potentials of Hibiscus sabdariffa anthocyanin extract.

The antioxidant and drug metabolizing potentials of Hibiscus anthocyanin extract in CCl(4)- induced oxidative damage of rat liver was investigated. Hibiscus anthocyanin extract effectively scavenge α-diphenyl-ß-picrylhydrazyl (DPPH) radical, superoxide ion, and hydrogen peroxide. It produced a 92% scavenging effect of DPPH radical at a concentration of 2.0 mg/mL. Hibiscus anthocyanin extract produced a 69 and 90% scavenging effect on superoxide ion and hydrogen peroxide, respectively, at 1.0 mg/mL, which compared favorably with the synthetic antioxidant (butylated hydroanisole and α-tocopherol). A reducing power of this anthocyanin was examined using K(3)Fe(CN)(6). Hibiscus anthocyanin extract has reducing power that is approximately 2-fold that of the synthetic antioxidant, butylated hydroanisole. Hibiscus anthocyanin extract produced a significantly increase and completely attenuated the CCl(4)-mediated decrease in antioxidant enzymes (e.g., catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase). However, the level of nonenzymic antioxidant molecules (i.e., vitamins C and E) were significant preserved by Hibiscus anthocyanin extract. There was an induction of phase II drug-detoxifying enzymes: glutathione S-transferase, NAD(H):quinone oxidoreductase, and uridyl diphosphoglucuronosyl transferase by 65, 45, and 57%, respectively. In view of these properties, Hibiscus sabdariffa anthocyanin extract can act as a prophylactic by intervening as a free radical scavenger both in vitro and in vivo as well as inducing the phase II drug detoxification enzymes.

Antioxidant and drug detoxification potential of aqueous extract of Annona senegalensis leaves in carbon tetrachloride-induced hepatocellular damage.

CONTEXT: Despite the myriad uses of Annona senegalensis Pers. (Annonaceae) leaves in folklore medicine of Nigeria, the basis is yet to be substantiated by scientific investigations. OBJECTIVES: To investigate the antioxidant (in vitro and in vivo) and drug detoxification potential of aqueous extract of A. senegalensis leaves in CCl4-induced hepatocellular damage. MATERIALS AND METHODS: In vitro antioxidant activity of the aqueous extract of A. senegalensis leaves was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, superoxide ion, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) and ferric ion models while in vivo antioxidant and drug detoxification activities of the extract at 100, 200, and 400 mg/kg body weight were done by assaying the levels of enzymic and non-enzymic indices in CCl4-induced hepatocellular damage. RESULTS: The extract at 1 mg/mL scavenged DPPH, H2O2, superoxide ion, and ABTS radicals, whereas ferric ion was significantly (P <0.05) reduced. The levels of alkaline and acid phosphatases, alanine and aspartate aminotransferases, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, reduced glutathione, vitamins C and E, glutathione S-transferase, nicotinamide adenine dinucleotide (reduced):Quinone oxidoreductase, uridyl diphosphoglucuronyl transferase, malondialdehyde, and lipid hydroperoxide that decreased in CCl4 treated animals were significantly attenuated by the extract in a manner similar to the animals treated with the reference drug. DISCUSSION AND CONCLUSION: The ability of the aqueous extract of A. senegalensis leaves to scavenge free radicals in vitro and reversal of CCl4-induced hepatocellular damage in rats suggest antioxidant and drug detoxification activities. Overall, this study has justified the rationale behind some of the medicinal uses of the plant in folklore medicine of Nigeria.

Acetaminophen perturbed redox homeostasis in Wistar rat liver: protective role of aqueous Pterocarpus osun leaf extract.

This study investigates the in vitro antioxidant potentials and attenuation of acetaminophen-induced redox imbalance by Pterocarpus osun Craib (Fabaceae) leaf in Wistar rat liver. The in vitro antioxidant activity of the extract (0.2-1.0 mg/mL) was evaluated using 2,2-diphenyl-1-picrylhydrazl (DPPH), hydrogen peroxide, superoxide ion, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate (ABTS), and ferric ion. The extract (150 and 300 mg/kg body weight) significantly (P<0.05) attenuated the altered liver and serum enzymes of acetaminophen treated animals. Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities as well as vitamins C and E, and glutathione levels were significantly (P<0.05) elevated by the extract. The activities of uridyl diphosphoglucuronosyl transferase (59%), quinone oxidoreductase (53%), and glutathione S-transferase (73%) significantly increased. The extract of P. osun leaf extract at 1.0mg/mL scavenged the DPPH, hydrogen peroxide, superoxide ion, and ABTS at 94, 98, 92, and 86%, respectively, while ferric ion was significantly reduced. There was attenuation of malondialdehyde and lipid hydroperoxide. The results indicates that P. osun leaves attenuated acetaminophen-induced redox imbalance, possibly acting as free radical scavenger, inducer of antioxidant and drug-detoxifying enzymes, which prevented/reduced lipid peroxidation.