Hydroethanolic extract of Psidium guajava leaf for induced osteoarthritis using a guinea pig model.

We investigated the therapeutic effects of an extract of Psidium guajava (guava) leaf on experimentally induced osteoarthritis in guinea pig. The left knee of 30 male guinea pigs was anesthetized and the cranial cruciate ligament was severed. The animals were followed for 8 weeks until osteoarthritis was confirmed by radiography and histopathology. Animals were divided randomly into five groups; group 1, the ligament was severed and untreated; group 2, the ligament was severed and treated with piascledine, an extract of soybean and avocado; group 3, the ligament was severed and treated with 200 mg/kg hydroethanolic extract of guava; group 4, the ligament was severed and treated with 400 mg/kg hydroethanolic extract of guava; and group 5, control animals without surgery or extracts. Radiological and histopathological evaluations after 8 weeks showed reduced severity of osteoarthritis in the piascledine treatment group compared to group 1. The guava extract also reduce the severity of osteoarthritis compared to controls. Histopathological examination of treatment and control groups showed that treatment the guava extract improved lesions significantly. Hydroethanolic extracts of guava leaf appears to prevent osteoarthritis by inhibition of free radical formation in the knee joint.

Evaluating the Role of Drug Metabolism and Reactive Intermediates in Trazodone-Induced Cytotoxicity toward Freshly-Isolated Rat Hepatocytes.

Background: Trazodone is an antidepressant agent widely administered for the treatment of depressive disorders. On the other hand, several cases of hepatic injury have been reported after Trazodone administration. Although the precise mechanism(s) of trazodone-induced liver injury is not known, some investigations proposed the role of reactive intermediates in this complication. This study was designed to investigate the role of reactive metabolites in hepatocytes injury induced by trazodone. Methods: Isolated rat hepatocytes were prepared by the method of collagenase enzyme perfusion via the portal vein. Cells were treated with trazodone, its cytotoxic metabolite, and different enzyme inhibitors and cytoprotective agents. Results: It was found that trazodone was toxic towards hepatocytes and caused 50% cell death after 2 h of incubation at a dose of 450 µM. The trazodone postulated reactive metabolite; m-chlorophenyl piperazine (m-CPP) was less toxic and caused 50% cell death at a dose of 750 µM at a similar time period. Cellular glutathione (GSH) depletion and lipid peroxidation were detected when hepatocytes were treated with trazodone and/or m-CPP. Depleting hepatocytes GSH beforehand, increased cytotoxicity of both trazodone and m-CPP. Troleandomycin as the CYP3A4 inhibitor prevented cytotoxicity of trazodone but slightly affected m-CPP-induced cell injury. Inhibition of CYP2D6 by quinidine and cimetidine increased the cytotoxicity of both trazodone and m-CPP. Antioxidants and ATP suppliers slightly prevented cytotoxicity of trazodone and m-CPP. Conclusion: As inhibitors of CYP3A4 and 2D6 affected trazodone cytotoxicity, it is suggested that trazodone -induced cytotoxicity, at least in part, is mediated by its reactive metabolites.

Antioxidant Effects of Bone Marrow Mesenchymal Stem Cell against Carbon Tetrachloride-Induced Oxidative Damage in Rat Livers.

BACKGROUND: Liver fibrosis results from excessive accumulation of extracellular matrix, which affects liver function over time and leads to its failure. In the past, liver transplant was thought to be the only treatment for end-stage liver disease, but due to the shortage of proper donors other medical treatments have been taken into consideration. OBJECTIVE: To evaluate the therapeutic effects of bone marrow derived mesenchymal stem cells (BM-MSC) in CCl4 damaged rats. METHODS: Liver damage in adult male Wistar rats was induced with carbon tetrachloride (CCl4). The rats were divided into normal control group, receiving CCl4, and those receiving CCl4 + marrow derived-MSC. Human BM-MSC was isolated, cultured, and characterized. The rats were injected with xenograft MSCs into the hepatic lobes of the liver. In the eighth week, blood samples were taken from all groups. Histological examination and biochemical analyses were used to compare the morphological and functional liver regeneration among different groups. Measurement of lipid peroxidation and glutathione transferase activity was also performed. RESULTS: Histopathology and biochemical analyses indicated that local injection of human BM-MSCs was effective in treating liver failure in the rat model. Furthermore, oxidative stress was attenuated by increased level of GSH content after MSC transplantation. CONCLUSION: Evidence of this animal model approach showed that bone marrow-derived MSCs promote an antioxidant response and support the potential of using MSCs transplantation as an effective treatment modality for liver disease.

The effects of fumaria parviflora L extract on chronic hand eczema: a randomized double-blind placebo controlled clinical trial.

BACKGROUND: Hand eczema is a common and distressing condition with multiple causes such as atopy, irritant and allergic contact dermatitis. Fumaria parviflora, is known as Shahtareh in Persian, is a folk medicine for eczema. This study aimed to evaluate the effect of alcoholic extract of Fumaria parviflora on hand eczema. METHODS: In a randomized double-blind, placebo-controlled study, 44 patients with hand eczema were randomly assigned to apply 4% cream of Fumaria parviflora or vehicle cream to hand twice daily for 4 weeks. RESULTS: The reduction of eczema area and severity index score before and two weeks after therapy was statistically significant between vehicle treated and in treated group. Only one patient showed side effects such as erythema and population. CONCLUSION: Fumaria parviflora appears to be tolerated by most patients and the findings showed that its extract may be considered as an effective agent for treatment of chronic hand eczema.

Caffeic acid, chlorogenic acid, and dihydrocaffeic acid metabolism: glutathione conjugate formation.

The antioxidant properties of the dietary dihydroxycinnamic acids [caffeic (CA), dihydrocaffeic (DHCA), and chlorogenic (CGA) acids] have been well studied but little is known about their metabolism. In this article, evidence is presented showing that CA, DHCA, and CGA form quinoids and hydroxylated products when oxidized by peroxidase/H(2)O(2) or tyrosinase/O(2). Mass spectrometry analyses of the metabolites formed with peroxidase/H(2)O(2)/glutathione (GSH) revealed that mono- and bi-glutathione conjugates were formed for all three compounds except CGA, which formed a bi-glutathione conjugate only when GSH was present. In contrast, the metabolism of the dihydroxycinnamic acids by tyrosinase/O(2)/GSH resulted in the formation of only mono-glutathione conjugates. In the absence of GSH, hydroxylated products and p-quinones of CA or CGA were formed by peroxidase/H(2)O(2). DHCA formed a hydroxylated adduct (even though GSH was present), as well as the corresponding p-quinone and dihydroesculetin, an intramolecular cyclization product. NADPH also supported rat liver microsomal-catalyzed CA-, CGA-, and DHCA-glutathione conjugate formation, which was prevented by benzylimidazole, a cytochrome P450 inhibitor. Furthermore, the cytotoxicity of CA, CGA, and DHCA toward isolated rat hepatocytes was markedly enhanced by hydrogen peroxide or cumene hydroperoxide-supported cytochrome P450 and was prevented by benzylimidazole. Cytotoxicity was also markedly enhanced by dicumarol, an NADPH/oxidoreductase inhibitor. These results suggest that dihydroxycinnamic acids were metabolically activated by P450 peroxidase activity to form cytotoxic quinoid metabolites.

Inhibitory effect of morphine on yawning induced by cholinoceptor and dopamine D2 receptor activation in rats.

1. Bromocriptine (2, 4 and 8 mg kg-1, i.p.), physostigmine (0.05, 0.1 and 0.2 mg kg-1, i.p.) and pilocarpine (1, 3 and 5 mg kg-1, i.p.) induced dose-dependent yawning in rats. 2. These responses were reduced in a dose-dependent manner by pretreatment with morphine. 3. The inhibitory effect of morphine was reversed by naloxone. 4. Naloxone alone induced slight but significant yawning. 5. The present results suggest that morphine inhibits yawning in rats at an opiate receptor downstream from the sites at which cholinoceptor and dopamine D2 activation induce yawning. The anatomical location of these sites remains to be established.