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Oral cancer is one of the most common cancers in the world. Drugs can modulate the expression of drug metabolizing enzymes and are useful in chemoprevention as well as therapy in cancer. 4-Nitroquinoline 1-oxide (4-NQO) is used to induce oral cancer in the present study. In the present investigation, the effect of green tea polyphenols (GTP) on the activities of cytochrome b5, cytochrome P450, cytochrome b5 reductase (cyt b5 R), cytochrome P450 reductase (cyt P450 R), arryl hydrocarbon hydroxylase (AHH), DT-diaphorase (DTD)(Phase I enzymes) and glutathione-S-transferase (GST) and UDP-glucuronyl transferase (UDP-GT) (Phase II enzymes) were assessed in tongue and oral cavity. In induced rats, there was a decrease in the activity of Phase II enzymes and an increase in the activity of Phase I enzymes. On supplementation of GTP by both simultaneous and post treatment mode (200 mg/kg) there was a significant increase in the activity of GST and UDP-GT and a significant decrease in the activity of Phase I enzymes. There was a significant decline in the number of tumors, tumor volume and oral squamous cell carcinoma in both simultaneous and post GTP treated animals relative to 4-NQO induced animals; on comparing simultaneous and post GTP treated animals the number of tumors, tumor volume and oral squamous cell carcinoma was significantly reduced in post treated animals. Thus inhibition of Phase I enzymes could be attributed to the protective efficacy of GTP which deactivates carcinogen and GTP induced the expression of Phase II enzymes that detoxifies the 4-NQO. It can be proposed that GTP plays role as a detoxifying agent by which its modulating role prevented/inhibited the formation of tumor.

Helicobacter pylori lipopolysaccharide (HP-LPS) is a potent virulence factor in the causation of gastric ulcer and gastritis. H. pylori-induced gastric pathology is prevalent throughout the world. Herbal medicines are attracting attention because of their traditional values, popularity and belief, as well as for their advantages such as less toxicity, affordability and medicinal value. The present study aimed to evaluate the anti-ulcer effect of a methanolic extract of Terminalia arjuna (TA) against HP-LPS-induced gastric damage in rats. Ulcers were induced with HP-LPS (50 μg per animal) administered orally daily for 3 days. The efficacy of TA on gastric secretory parameters such as volume of gastric juice, pH, free and total acidity, pepsin concentration, and the cytoprotective parameters such as protein-bound carbohydrate complexes in gastric juice and gastric mucosa was assessed. The protective effect of TA was also confirmed by histopathological examination of gastric mucosa. HP-LPS-induced alterations in gastric secretory parameters were altered favourably in rats treated with TA, suggesting that TA has an anti-secretory role. Furthermore, HP-LPS-induced impairments in gastric defence factors were also prevented by treatment with TA. These results suggest that the severe cellular damage and pathological changes caused by HP-LPS are mitigated by TA; these effects are comparable with those of sucralfate. The anti-ulcer effect of TA may reflect its ability to combat factors that damage the gastric mucosa, and to protect the mucosal defensive factors.

Mitochondria play a central role in molecular events leading to tissue damage in ischemia. The present study examines the role of the alcoholic extract of T. chebula (TCE) pretreatment (50 mg/100 g body weight) to attenuate the isoproterenol (ISO) (20 mg/100 g body wt, sc) induced alterations on heart mitochondrial ultrastucture and function in experimental rats. ISO induced cardiotoxicity was evidenced by a significant rise in the level of lactate, decrease in enzyme activities of tricarboxylic acid cycle (TCA), mitochondrial respiration, levels of adenosine triphosphate (ATP) and oxidative phosphorylation. TCE intervention significantly attenuated the above alterations by ISO and retained near normal function of the mitochondria. Electron microscopic studies of the mitochondria further support the isoproterenol induced deleterious changes and accredit the protective effect of TCE on mitochondrial structure and energy metabolism.

Etiology of gastric ulceration is multifactorial. Reserpine, a hypertensive drug, causes cholinergically mediated gastric damage as a side effect. The ethanol extract of Pterocarpus santalinus. L.f. (Fabaceae) (PSE) has been evaluated in this study for its ability to serve as a gastroprotective agent in reserpine-induced, pyloric-ligated experimental rats. Dose of 50–250 mg/kg of PSE showed a significant inhibition (p < 0.01, p < 0.001) of lesion index when compared with reserpine, and the effective dose was found to be 150 mg/kg. A significant reduction in gastric volume, free acidity, total acidity, and pepsin concentration has been observed on PSE treatment. SDS-PAGE showed an increased expression of mucin on account of a decreased proteolytic cleavage due to decreased peptic activity. PSE increased the carbohydrate to protein ratio. Further, PSE prevented the depletion of phospholipids and stimulated cell proliferation, thus playing a role in mucosal defense. This gastroprotective effect of PS...

Solanum nigrum, an herbal plant which is recommended in ayurveda for the management of gastric ulcers. Therefore, the purpose of the study was to investigate the antiulcer effect of Solanum nigrum fruits extract (SNE) on cold restraint stress (CRU), indomethacin (IND), pyloric ligation (PL) and ethanol (EtOH) induced gastric ulcer models and ulcer healing activity on acetic acid induced ulcer model in rats. The treatment with SNE at higher dose significantly inhibited the gastric lesions induced by CRU (76.6%), IND (73.8%), PL (80.1%) and EtOH (70.6%), respectively, with equal or higher potency than omeprazole. SNE showed concomitant attenuation of gastric secretory volume, acidity and pepsin secretion in ulcerated rats. In addition, SNE (200 and 400mg/kgb.w.) accelerated the healing of acetic acid induced ulcers after the treatment for 7 days. Further, to ascertain the antisecretory action, the effects of SNE on H(+)K(+)ATPase activity and plasma concentration of gastrin hormone in ulcerated rats were determined. SNE significantly inhibits H(+)K(+)ATPase activity and decreases the gastrin secretion in EtOH-induced ulcer model. The severity of the reaction of ulcerogen and the reduction of ulcer size by SNE was evident by histological findings. Toxicity studies of SNE have also been carried out for its safety evaluation. SNE, thus, offers antiulcer activity by blocking acid secretion through inhibition of H(+)K(+)ATPase and decrease of gastrin secretion. These results further suggest that SNE was found to possess antiulcerogenic as well as ulcer healing properties, which might also be due to its antisecretory activity.

Despite a strong association between cigarette smoking and alarming increase in mortality rate from smoking-related diseases, around 35–40% of the world's population continues to smoke and many more are being exposed to environmental tobacco smoke. Since the role of free radicals and oxidative damage in the pathogenesis of smoking-related diseases has been suggested, bacoside A, a potent antioxidant was tested for its ability to protect against cigarette smoking-induced toxicity in terms of lactate dehydrogenase (LDH) and its isoenzymes. Rats were exposed to cigarette smoke and simultaneously administered with bacoside A, for a period of 12 weeks. Total LDH activity was assayed in serum, lung, heart, brain, liver and kidney, and serum LDH isoforms were separated electrophoretically. Cigarette smoke exposure resulted in significant increase in serum LDH and its isoenzymes with a concomitant decrease in these organs. These alterations were prevented by administration of bacoside A. Excessive oxidants from cigarette smoke is known to cause peroxidation of membrane lipids leading to cellular damage, thereby resulting in the leakage of LDH into the circulation. Bacoside A could have rendered protection to the organs by stabilizing their cell membranes and prevented the release of LDH, probably through its free radical scavenging and anti-lipid peroxidative effect.

Reactive oxygen species, neutrophil infiltration and pro-inflammatory cytokines play an important role in the pathogenesis of gastric ulcers caused by aspirin. The present study demonstrates the healing effect of Cissus quadrangularis extract (CQE) through inhibitory action on generation of lipid peroxidation, proinflammatory cytokines and neutrophil infiltration. The concentration of malondialdehye (MDA), protein carbonyl content, conjugated dienes, mucosal (SH) sulphydryls, uric acid, tumor necrosis factor-alpha (TNF-cc), and activities of myelo-peroxidase (MPO), xanthine oxidase (XO) and antioxidative enzymes were determined in the gastric mucosa. Administration of CQE significantly attenuated the gastric lesions induced by aspirin and this was accompanied by the rise in uric acid, antioxidative enzymes, SH groups, and a significant decrease in lipid peroxidase, TNF-oc, MPO and XO activities. These findings suggest that the significant gastroprotective activity could be mediated by the antioxidant acti...

Chronic exposure to cigarette smoke affects the structure and function of mitochondria, which may account for the pathogenesis of smoking-related diseases. Bacopa monniera Linn., used in traditional Indian medicine for various neurological disorders, was shown to possess mitrochondrial membrane-stabilizing properties in the rat brain during exposure to morphine. We investigated the protective effect of bacoside A, the active principle of Bacopa monniera, against mitochondrial dysfunction in rat brain induced by cigarette smoke. Male Wistar albino rats were exposed to cigarette smoke and administered bacoside A for a period of 12 weeks. The mitochondrial damage in the brain was assessed by examining the levels of lipid peroxides, cholesterol, phospholipid, cholesterol/phospholipid (C/P) ratio, and the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, and cytochrome C oxidase. The oxidative phosphorylation (rate of succinate oxidation, respiratory control ratio and ADP/O ratio, and the levels of ATP) was evaluated for the assessment of mitochondrial functional capacity. We found significantly elevated levels of lipid peroxides, cholesterol, and C/P ratio, and decreased levels of phospholipids and mitochondrial enzymes in the rats exposed to cigarette smoke. Measurement of oxidative phosphorylation revealed a marked depletion in all the variables studied. Administration of bacoside A prevented the structural and functional impairment of mitochondria upon exposure to cigarette smoke. From the results, we suggest that chronic cigarette smoke exposure induces damage to the mitochondria and that bacoside A protects the brain from this damage by maintaining the structural and functional integrity of the mitochondrial membrane.

We studied the anti-hepatotoxic potential of Liv.100, a herbal formulation, on anti-tubercular (anti-TB) drugs [isoniazid (INH), rifampicin (RMP), and pyrazinamide (PZA)]-induced mitochondrial damage in rat liver. Liv.100 (400mg/kg body wt./day, orally) was administered simultaneously with anti-TB drugs for 6 weeks. Activities of TCA cycle enzymes (succinate dehydrogenase, isocitrate dehydrogenase, malate dehydrogenase, and α-ketoglutarate dehydrogenase) and respiratory marker enzymes (cytochrome c oxidase, NADH dehydrogenase) and levels of mitochondrial lipid peroxidation in liver were determined. Activities of TCA cycle enzymes and respiratory marker enzymes were significantly lower upon anti-TB drug treatment than those of normal controls. Mitochondrial lipid peroxidation was found to be increased when compared with the normal control value. This indicates impaired function of hepatic mitochondria in anti-TB drug-induced hepatocellular damage. In our present study, Liv.100 co-administration significantly reduced the anti-TB drug-induced alterations in the level of lipid peroxide and activities of TCA cycle enzymes and respiratory marker enzymes in liver mitochondria. The mechanism of action of Liv.100 is probably due to its antioxidant nature against anti-TB drug-induced lipid peroxidation, which is mainly responsible for the inhibition of these enzyme activities.

Oral submucous fibrosis (OSMF), a disease condition essentially found in Indians and southeast Asians has drawn attention mostly on the grounds of epidemiological and clinical manifestations, whereas the etiology is still uncertain. Since all OSMF patients are habitual chewers, it was thought ideal to experimentally induce OSMF in rats using betelnut extracts thereby establishing the toxic nature of betelnut. OSMF has been defined as a collagen disorder and the total collagen and collagen fractions in the different groups were analyzed. There was an increase in total collagen content and an increase in soluble fraction was also observed representing newly synthesized collagen. The group treated with panmasala, a commercial preparation available which is a combination of betelnut, tobacco, lime and spices showed no changes due to its chemopreventive efficacy. The importance of the results expected is that the causation and cure of many diseases involving collagen now lack a scientific basis. The results it is hoped would provide a means for classification of diseases at structural and molecular level so as to highlight a causal nexus between clinical expression of the disease and altered structural and compositional changes in OSMF.

The present investigation was performed to study the effect of Liv.100, an ayurvedic herbal formulation, on the level of lipids in antabuse-using alcohol dependents. Liv.100 was given to the patients at the dosage of 35 mg/kg body wt for a period of 18 days. Antabuse-treated patients received antabuse at 4 mg/kg body wt dosage for a period of 18 days. Fasting blood samples were collected before and after treatment of 18 days and used for the estimation of total lipids, total cholesterol, triglycerides, phospholipids, free fatty acids, free cholesterol, and ester cholesterol. The antabuse-receiving alcohol dependents treated with Liv.100 showed significant decreases in the levels of total lipids, total cholesterol, triglycerides, free cholesterol, and ester cholesterol when compared with alcohol dependents receiving antabuse alone. The present study suggests the hypolipidemic effect of Liv.100 in antabuse-using alcohol dependents.

Oral submucous fibrosis (OSMF) is a chronic disease of obscure etiology affecting any part of the oral cavity. Several histologic and epidemiologic studies on this condition have been conducted, but the biochemical aspects have not yet been thoroughly explored. Hence we analyzed the clinically important enzymes in OSMF patients. They were divided into three groups according to the degree of severity of the disease. There was a significant increase in the activities of phosphatases, transaminases, aldolase, 5'-nucleotidase, and y-glutamyl transpeptidase in OSMF patients as compared with normal subjects. The increase correlated well with the progression of the disease, being the highest in the advanced stage where patients had co-existing carcinoma. The results, it is hoped, will provide a means for classification of diseases at the structural and molecular level so as to highlight a causal nexus between clinical expression of the disease and altered structural and compositional changes in OSMF.

The protective effect of α-tocopherol pretreatment on antioxidant status in erythrocytes of isoproterenol-induced myocardially infarcted rats was studied. Isoproterenol-treated rats showed a significant decrease in the activity of erythrocyte antioxidant enzymes, resulting in increased lipid peroxides in serum and erythrocytes. The level of antioxidants such as vitamin E, ascorbate, and glutathione decreased on isoproterenol treatment. α-Tocopherol pretreatment prevented the inactivation of erythrocyte antioxidant enzymes and formation of lipid peroxides. The antioxidant levels were maintained near normal in α-tocopherol-pretreated, isoproterenol-administered rats. α-Tocopherol, being a potential antioxidant, reduces free radical-mediated reactions, thereby preventing erythrocyte damage.

Oral submucous fibrosis is a chronic disease of obscure etiology affecting the oral cavity. Several histologic and epidemiologic studies on this condition have been conducted, but the biochemical aspects have not yet been thoroughly explored. Hence the present study was undertaken to study the hematological status and trace elements in this condition. There was no change in the cell count, whereas increases in platelet count, eosinophil number, and erythrocyte sedimentation rate were observed. There was a significant decrease in the levels of hemoglobin, iron, ceruloplasmin, copper and zinc; and they correlated well with the progression of the disease. Consideration of these findings should open new avenues for exploration of the disease from new perspectives.

The present study evaluated the protective effect of fish oil in isoproterenol-induced myocardial infarction in rats. The results of the present study indicate that the IPH administration decreases the activities of membrane-bound ATPases compared to control animals. Fish oil pretreatment brought about significant increase in the activity of these membrane-bound ATPases in IPH (isoproterenol hydrochloride)-treated animals. Significant increase in serum potassium level with concomitant decrease in the values of sodium, magnesium, and calcium were observed in IPH-treated rats compared to control rats, fish oil pretreatment reversed these changes to near normal. Significant elevation of sodium and calcium levels with concomitant decrease in the levels of potassium and magnesium were observed in the myocardial tissue of IPH-administered rats compared to control rats, fish oil pretreatment followed by IPH administration brought these levels to near normal. The levels of lipid peroxidation (LPO) in both serum and tissue were increased in IPH-treated rats compared with control rats, whereas pretreatment with fish oil in IPH-treated rats maintained near-normal LPO levels. The results of the present study reveals that the pretreatment of fish maintains the activities of membrane-bound ATPases and the mineral levels at near normal by the inhibition of lipid peroxidation.

Terminalia chebula is an ayurvedic drug recommended for the treatment of heart diseases. Earlier studies by the authors validated the beneficial cardioprotective effect of T chebula against isoproterenol-induced myocardial infarction.To evaluate the therapeutic efficacy of T chebula in protecting against isoproterenol-induced lysosomal membrane damage.Lysosomal enzyme activities from the serum, heart and lysosomal fractions were determined. The triphenyltetrazolium chloride assay was used to confirm the protective effect of T chebula on the myocardium.Isoproterenol administration produced significant cardiac damage (as seen by the triphenyltetrazolium chloride assay) and significantly altered lysosomal enzyme activities. Pretreatment with an ethanol extract of T chebula was found to retain near normal activities of lysosomal enzymes in rats given T chebula or T chebula plus isoproterenol compared with rats given isoproterenol alone.Pretreatment with T chebula extract stabilizes the lysosomal membrane and, thus, may have prevented myocardial damage.

Aim The present study was aimed to evaluate the effect of methanolic extract of Terminalia arjuna (TA) on diclofenac sodium induced gastric ulcer in experimental rats. Methods Animals were induced for gastric ulcer with diclofenac sodium (DIC) (80 mg/kg bodyweight in water, orally) and treated orally with TA in various doses ranging from 100 mg/kg bodyweight to 500 mg/kg bodyweight. The effective dose was 400 mg/kg bodyweight, since this dose elicited a maximum reduction in lesion index. The gastroprotective effect of TA was assessed from volume of gastric juice, pH, free and total acidity, pepsin concentration, acid output in gastric juice, the levels of non-protein sulfhydryls (NP-SH), lipid peroxide (LPO), reduced glutathione (GSH), and activities of enzymic antioxidants—super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and myeloperoxidase (MPO) in gastric mucosa. The levels of DNA, protein bound carbohydrate complexes—hexose, hexoseamine, sialic acid, fucose in gastric mucosa and gastric juice and the levels of RNA in gastric mucosa were assessed. The stomach tissues were used for adherent mucus content and also for the histological examination. Results A significant reduction in lesion index was observed in ulcer induced animals treated with TA (DIC + TA) compared to ulcerated rats (DIC). A significant increase was observed in pH, NP-SH, GSH, enzymic antioxidants, protein bound carbohydrate complexes, adherent mucus content, nucleic acids with a significant decrease in volume of gastric juice, free and total acidity, pepsin concentration, acid output, LPO levels and MPO activities in DIC + TA rats compared to DIC rats. Histological studies confirmed the gastroprotective activity of TA. Conclusion From the data presented in this study it could be concluded that T. arjuna acts as an gastroprotective agent probably due to its free radical scavenging activity and cytoprotective nature.

The objective of this research was to analyse the gastroprotective effect of Cissus quadrangularis extract (CQE) along with its mechanism underlying the therapeutic action against the gastric mucosal damage induced by aspirin. In this study, we investigated the effect of CQE on the course of experimentally induced gastric ulcer by analyzing the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), microvascular permeability, activity of nitric oxide synthase-2 (NOS-2), mitochondrial antioxidants, lipid peroxidation and DNA damage. A significant increase in vascular permeability, NOS-2 activity, TNF-alpha, IL-1beta levels and oxidative damage were noted in aspirin administered rats. Pretreatment with CQE (500 mg/kg bw/day) by oral gavage for 7 days significantly attenuated these biochemical changes caused by aspirin in rats. Tissue damage was showed by decreased levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) and an associated rise in lipid peroxidation (LPO) in mitochondria, which were reversed by CQE. In addition, CQE prevents oxidative damage of DNA by reducing DNA fragmentation indicating its block on cell death. Ulcer protection in CQE treated rats was confirmed by histoarchitecture, which was comprised of reduced size of ulcer crater and restoration of mucosal epithelium. Thus, reduced neutrophil infiltration, antiapoptotic and antioxidant action have a pivotal role in the gastroprotective effect of CQE.

In human breast cancer MCF 7 cells, the effect of exogenous histone H1 on intracellular calcium ([Ca2+]i) levels was measured using Fura 2AM. The dose and time dependent assessment revealed significant cell killing effect of histone H1 on MCF 7 cells. Histone H1 induced a sustained concentration dependent increase in [Ca2+]i levels in the presence of calcium in the medium, but the increase was reduced in the absence of extra cellular calcium. The effect of histone H1 on intracellular calcium flux measured using 45Ca radiolabel revealed significant inhibition of calcium uptake in endoplasmic reticulum, whereas the rate of uptake was unaltered in the mitochondria. The activities of phospholipase A2 showed a significant transient increase at 1 minute which by the end of 5 minutes decreased, whereas the activities of phospholipase C which showed a transient increase at the end of 1 minute, was maintained at basal levels in histone H1 treated cells compared to control cells. These findings suggest that histone H1 increases [Ca2+]i in MCF 7 cells by stimulating both extra cellular calcium influx and intracellular calcium release at higher concentrations exhibiting cytotoxic effect.

Colonic cell proliferation is the prerequisite for the genesis of cancer. Experimental and epidemiologic evidence indicate dietary factors to be one of the commonest predisposing factors in the development of several types of cancers including large intestine. Here we have investigated the role of the fruit pulp of Tamarindus indica L. (TI), a tropical plant-derived food material, on the proliferating colonic mucosa using Swiss albino mice. Crypt cell proliferation rate (CCPR), on histological basis and [3H]-thymidine incorporation assay were chosen to evaluate the modulating potential of TI per se and in response to a subacute dose of N-nitroso N'-methyl urea (MNU). Descending colonic segment showed greater rate of cell proliferation than the ascending colon and cecum tissues isolated from the group 2 (TI-per se) when compared with group 1 (negative controls). It also revealed a positive correlation with the incorporation studies. Significant increase in the CCPR and radiolabeled precursor incorporation (p0.001) was observed in MNU-induced+TI fed group of animals (group 4) in all the three segments when compared with control diet fed normal (group 1) as well as MNU-induced (group 3) animals. This study therefore indicates a co-stimulatory effect of TI on MNU-induced colonic cell kinetics.