Anti-arthritic and anti-inflammatory activity of combined pioglitazone and prednisolone on adjuvant-induced arthritis.

The aim of the present study was to evaluate the effect of combined treatment of pioglitazone (PGZ) and prednisolone (PDL) on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritis was induced by single intra-dermal injection of 0.1 ml Freund's complete adjuvant (0.05% w/v Mycobacterium butyricum in mineral oil) into foot pads of left hind paws of Wistar rats of either sex. There were six experimental groups: Group I was healthy animals as control, Group II was arthritic animals without drug treatment, Group III was arthritic animals treated with a standard non-steroidal anti-inflammatory drug aspirin (100 mg/kg), Group IV was arthritic animals received PGZ (10 mg/kg) alone, Group V was arthritic animals received PDL (10 mg/kg) alone, and Group VI was arthritic animals treated with a combined suspension of PGZ and PDL (20 mg/kg). Drugs were administered daily orally at day 0 and continued upto 28th day after induction of arthritis. Induction of arthritis significantly increased hind paw volume (HPV), loss of body weight (BW), enhanced tibiotarsal joint thickness (TJT), and increased plasma tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 levels. Treatment with aspirin or combined suspension of PGZ and PDL in the arthritic animals produced significant reductions in HPV and TJT, normalized BW, and significantly decreased plasma levels of TNF-α and IL-6. These observations suggest that the combined administration of PGZ and PDL was effective in modulating the inflammatory response and suppress arthritis progression in experimental animal model. These findings may help to improve the treatment of rheumatoid arthritis.

Protective role of curcumin on colchicine-induced cognitive dysfunction and oxidative stress in rats.

Dementia is a syndrome of progressive nature, affects wide range of cognitive abilities like memory, language, calculation and so on, neuropsychiatric and social deficits to impair the routine social functions. The present study was designed to assess the effect of curcumin against colchicine-induced cognitive dysfunction and oxidative stress in rats and compare it with rivastigmine. Colchicine (15 µg/5µl) was administered to male Wistar rats intracerebroventricularly (i.c.v.) by stereotaxic apparatus to induce cognitive dysfunction. Administration of colchicine caused poor retention of memory in elevated plus maze, passive avoidance apparatus and Morris water maze paradigms. Chronic treatment with curcumin (100, 200 and 400 mg/kg, p.o.) twice daily and rivastigmine (2.5 mg/kg, p.o.) daily for a period of 28 days beginning 7 days prior to colchicine injection significantly improved colchicine-induced cognitive impairment. Biochemical assessment revealed that i.c.v. colchicine injection significantly increased lipid peroxidation, depleted reduced glutathione levels and decreased acetyl cholinesterase (AChE) activity in rat brains. Chronic administration of curcumin significantly reduced the elevated lipid peroxidation, restored the reduced glutathione levels and AChE activity; however, rivastigmine failed to prevent oxidative stress. The results of the current study indicate that curcumin (100, 200 and 400 mg/kg, p.o.) twice daily has a protective role against colchicine-induced cognitive impairment and associated oxidative stress.

Propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function: attenuation by Withania somnifera.

Propoxur (2-isopropoxyphenyl N-methylcarbamate) is widely used as an acaricide in agriculture and public health programs. Studies have shown that sub-chronic exposure to propoxur can cause oxidative stress and immuno-suppression in rats. Carbamates are also known to exhibit inhibitory effect on cholinesterase activity, which is directly related to their cholinergic effects. In the present study, the effect of Withania somnifera (Ashwagandha), a widely used herbal drug possessing anti-stress and immunomodulatory properties was studied on propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function in rats. Male Wistar rats were divided into four groups. Group I was treated with olive oil and served as control. Group II was administered orally with propoxur (10 mg/kg b.wt.) in olive oil, group III received a combination of propoxur (10 mg/kg b.wt.) and W. somnifera (100 mg/kg b.wt.) suspension and group IV W. somnifera (100 mg/kg b.wt.) only. All animals were treated for 30 days. Cognitive behaviour was assessed by transfer latency using elevated plus maze. Blood and brain acetylcholine esterase (AChE) activity was also assessed. Oral administration of propoxur (10 mg/kg b.wt.) resulted in a significant reduction of brain and blood AChE activity. A significant prolongation of the acquisition as well as retention transfer latency was observed in propoxur-treated rats. Oral treatment of W. somnifera exerts protective effect and attenuates AChE inhibition and cognitive impairment caused by sub-chronic exposure to propoxur.

Influence of dietary ginger (Zingiber officinales Rosc) on antioxidant defense system in rat: comparison with ascorbic acid.

Ginger (Z. officinale; 1% w/w) significantly lowered lipid peroxidation by maintaining the activities of the antioxidant enzymes--superoxide dismutase, catalase and glutathione peroxidase in rats. The blood glutathione content was significantly increased in ginger fed rats. Similar effects were also observed after natural antioxidant ascorbic acid (100 mg/kg, body wt) treatment. The results indicate that ginger is comparatively as effective as ascorbic acid as an antioxidant.

Influence of dietary ginger (Zingiber officinales Rosc) on oxidative stress induced by malathion in rats.

Pesticide chemicals may induce oxidative stress leading to generation of free radicals and alterations in antioxidants or oxygen free radical (OFR) scavenging enzymes. Hence, the effect of subchronic malathion (O,O-dimethyl-S-1,2, bis ethoxy carbonyl ethyl phosphorodithioate) exposure was evaluated on lipid peroxidation, glutathione and related enzymes and OFR scavenging enzymes in albino rats. Administration of malathion (20 ppm) for 4 weeks increased the malondialdehyde (MDA) levels in serum, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in erythrocytes and glutathione reductase (GR) and glutathione S-transferase (GST) in serum. However, it decreased the glutathione (GSH) level in whole blood. Concomitant dietary feeding of Zingiber officinales Rosc (ginger 1%, w/w) significantly attenuated malathion induced lipid peroxidation and oxidative stress in these rats. These results indicate the possible involvement of free radicals in organophosphate-induced toxicity and highlight the protective action of ginger, an indigenous medicinal plant product.

Evaluation of oxidative stress in some cases of argimone oil poisoning during a recent outbreak of epidemic dropsy in India.

The study was designed to evaluate the oxidative stress and modulation of anti-oxidant enzymes in 10 accidental argimone oil poisoning cases admitted in a hospital in Delhi, India during a recent outbreak of epidemic dropsy in 1998. Serum malondialdehyde (MDA) level, oxygen free-radical scavenging enzymes such as superoxide dismutase (SOD) and catalase (CAT), and glutathione (GSH) and related enzymes, e.g. glutathione reductase (GR), glutathione peroxidase (GPx), gamma glutamyl transpeptidase (GGT) and glutathione-S-transferase (GST) in erythrocytes were assayed. The sanguinarine level in serum was measured by high-performance liquid chromatography. The serum MDA level was higher and the GSH level in erythrocytes was lower in argimone oil poisoning cases than those in controls. There was a significant decrease in SOD and GPx activities in erythrocytes of epidemic dropsy cases but no changes were observed in CAT, GR and GST assay. The depletion of GSH in erythrocytes, serum MDA level and clinical severity were dependent on serum sanguinarine level. The results indicate that sanguinarine (argimone oil) poisoning creates an oxidative stress in humans. The oxidative stress and differential modulation of anti-oxidant enzymes by sanguinarine might play a pathogenic role in epidemic dropsy, which suggests the incorporation of anti-oxidant drugs in the treatment protocol of the disease.

Modulation of humoral and cell-mediated immune responses by Azadirachta indica (Neem) in mice.

The effects of A. indica (AI, Neem) were evaluated on tests of humoral and cell-mediated immune responses after 3 weeks of oral AI (leaf extract) treatment in ovalbumin immunized mice. At the dose levels tested, AI (10, 30 or 100 mg/kg), had no appreciable influence on different organ (liver, spleen, thymus)/body weight indices, when compared to controls. In tests for humoral immune responses, AI (100 mg/kg) treated mice had higher (1) IgM and IgG levels, and (b) anti-ovalbumin antibody titres, when compared to the vehicle treated group. In tests for cell-mediated immune responses, there was an enhancement (%) of (a) macrophage migration inhibition, and (b) footpad thickness after AI (100 mg/kg) treatment. These results are discussed in light of the possible immunopotentiating effects of AI.