M. Raza

Gastric antiulcer and cytoprotective effect of Commiphora molmol in rats

The aqueous suspension of Commiphora molmol (oleo-gum resin) has been screened for its potential to protect gastric mucosa against the ulcers caused by 80% ethanol, 25% NaCl, 0.2 M NaOH, indomethacin and combined indomethacin-ethanol treatment. C. molmol pretreatment at doses of 250, 500 and 1000 mg/kg provided dose-dependent protection against the ulcerogenic effects of different necrotizing agents used. The effects caused by ethanol were further investigated. Treatment of rats with 1 ml of 80% ethanol was found to cause depletion of stomach wall mucus, reduction in the concentration of protein, nucleic acids and NP-SH groups in the stomach wall. Ethanol treatment also caused histopathological lesions including necrosis, erosion, congestion and haemorrhage of the stomach wall. Pretreatment with C. molmol offered a dose-dependent protection against all these effects. In the same manner it affected the malondialdehyde concentration altered by ethanol treatment. C. molmol also offered protection against mucosal damage caused by indomethacin and its combination with ethanol. The protective effect of C. molmol observed in the present study is attributed to its effect on mucus production, increase in nucleic acid and non-protein sulfhydryl concentration, which appears to be mediated through its free radical-scavenging, thyroid-stimulating and prostaglandin-inducing properties.

A comparison of hepatoprotective activities of aminoguanidine and N-acetylcysteine in rat against the toxic damage induced by azathioprine

Azathioprine (AZA) is an important drug used in the therapy of autoimmune system disorders. It induces hepatotoxicity that restricts its use. The rationale behind this study was the proven efficacy of N-acetylcysteine (NAC; a replenisher of sulfhydryls) and reports on the antioxidant potential of aminoguanidine (AG; an iNOS inhibitor), that might be useful to protect against the toxic implications of AZA. AG (100 mg/kg; i.p.) or NAC (100 mg/kg; i.p.) were administered to the Wistar male rats for 7 days and after that AZA (15 mg/kg, i.p.) was given as a single dose. This caused an increase in the activity of hepatic aminotransferases (AST and ALT) in the serum 24 h after AZA treatment. AZA (7.5 or 15 mg/kg, i.p.) also caused an increase in rat liver lipid peroxides and a lowering of reduced glutathione (GSH) contents. In the other part of experiment, protective effects of AG and NAC were observed on AZA induced hepatotoxicity. NAC significantly protected against the toxic effects produced by AZA. Pretreatment with NAC prevented any change in the activities of both the aminotransferases after AZA. This pretreatment also resulted in a significant decline in the contents of lipid peroxides and a significant elevation in GSH level was evident after AZA treatment. In the group with AG pretreatment the activities of AST and ALT did not increase significantly after AZA when compared to control. However, the lipid peroxides and GSH levels did not have any significant difference when compared to AZA group. These observations also indicate that the improvement in the GSH levels by NAC is the most significant protective mechanism rather than any other mechanistic profile. The protective effect of AG against the enzyme leakage seems to be through the liver cell membrane permeability restoration and is independent of any effects on liver GSH contents.

Boric acid enhances in vivo Ehrlich ascites carcinoma cell proliferation in Swiss albino mice

The influence of boric acid, a boron carrier, on Ehrlich ascites carcinoma (EAC) cell-bearing mice was investigated in view of its importance in the boron neutron capture therapy and the influence of boron on proliferation and progression of cancer cells mediated by proteoglycans and collagen. The present study included the evaluation of boric acid for the effects on total count and viability of EAC cells in addition to their non-protein sulfhydryls (NP-SH) and malondialdehyde (MDA) contents as parameters for conjugative detoxication potency and possible oxidative damage. The EAC cell-bearing animals were also observed for the effect on survival, body weight changes, and histopathological evaluation of the tumors grown at the site of inoculation. The treatment with boric acid significantly increased the total number of peritoneal EAC cells and their viability. A significant increase in the body weight was observed that dose-dependently reached plateau levels by 20 days of treatment. Conversely, a reduction in the duration of survival of these animals was evident with the same protocol. Boric acid treatment resulted in a decrease in NP-SH contents with a concomitant increase in MDA levels in EAC cells as revealed by the results of the biochemical analysis. These data are supported by our results on histopathological investigations, which apparently showed fast growth, in addition to several mitotic figures and mixed inflammatory reaction, after treatment with boric acid. It seems likely that a particular combination of properties of boric acid, rather than a single characteristic alone, will provide useful information on the use of this boron carrier in neutron capture therapy.

Evaluation of the genotoxic, cytotoxic, and antitumor properties ofCommiphora molmol using normal and Ehrlich ascites carcinoma cell-bearing Swiss albino mice

The genotoxic, cytotoxic and antitumor properties ofCommiphora molmol (oleo gum resin) were studied in normal and Ehrlich ascites carcinoma cell-bearing mice. In normal mice, the genotoxic and cytotoxic activity was evaluated on the bases of the frequency of micronuclei and the ratio of polychromatic to normochromatic cells in bone marrow, which was substantiated by the biochemical changes in hepatic cells. The antitumor activity ofC. molmol was evaluated from the total count and viability of Ehrlich ascites carcinoma cells and their nucleic acid, protein, malondialdehyde, and elemental concentrations in addition to observations on survival and the trend of changes in body weight. The tumors at the site of injection were evaluated for histopathological changes. Treatment withC. molmol (125–500 mg/kg) showed no clastogenicity but was found to be highly cytotoxic in normal mice. The results obtained in the Ehrlich ascites carcinoma cell-bearing mice revealed the cytotoxic and antitumor activity ofC. molmol which was found to be equivalent to those of the standard cytotoxic drug cyclophosphamide. On the basis of the nonmutagenic, antioxidative, and cytotoxic potential ofC. molmol as observed in the present study, its use in cancer therapy seems to be appropriate and further investigations are suggested.

Anticarcinogenic Effect of Commiphora molmol on Solid Tumors Induced by Ehrlich Carcinoma Cells in Mice

The anticarcinogenic potential of Commiphora molmol (oleoresin) was studied in Ehrlich-solid-tumor-bearing mice. The antitumor activity of C. molmol was evaluated from the total count and viability of Ehrlich solid tumor cells and their nucleic acid, protein, malondialdehyde and glutathione levels at the end of 25 and 50 days of treatment. Furthermore, observations of animal survival rate and measurements of the tumor and body weight were made. The Ehrlich solid tumors were also evaluated for histopathological changes. Treatment with C. molmol (250 and 500 mg/kg/day) was found to be cytotoxic in Ehrlich solid tumors cells. The antitumor potential of C. molmol was comparable to the standard cytotoxic drug cyclophosphamide. This effect of C. molmol was less pronounced after 50 days of treatment. The present study confirmed the cytotoxic and anticarcinogenic potential of C. molmol. Further studies are warranted to explore its mode of action and safety for medicinal use in cancer therapy.

Effect of Desferrioxamine on Cisplatin-induced Nephrotoxicity in Normal Rats

Biochemical and histological evaluations of the effects of the iron chelator desferrioxamine on the nephrotoxicity induced by cisplatin in normal rats were carried out. A single dose of cisplatin (7.5 mg/kg, intravenously) caused nephrotoxicity that manifested biochemically as an elevation of blood urea nitrogen, serum creatinine and an increase in the kidney weight as a percent of body weight. Moreover, severe decreases in serum calcium and albumin were observed. Histopathological examination of kidney tissue revealed tubular necrosis with sloughing of tubular epithelium. Desferrioxamine treatment (250 mg/kg, intraperitoneally) 30 min before cisplatin administration does not protect the kidney from the damaging effects of cisplatin. A greater increase in blood urea nitrogen, serum creatinine and kidney weight was observed with significant tubular necrosis and a mild lymphocytic infiltrate. Desferrioxamine pretreatment decreased the lipid peroxidation induced by cisplatin but at the same time increased nonprotein sulfhydryl (-SH) concentrations in the kidney tissue. The findings of this study suggest that lipid peroxidation is not the main cause of cisplatin-induced nephrotoxicity and that desferrioxamine which was useful for prevention of cardiac and hematological damage induced by doxorubicin, aggrevated the cisplatin-induced nephrotoxicity. More investigations are needed to establish a definite assessment of its selectivity.

Potentiation of diclofenac-induced anti-inflammatory response by aminoguanidine in carrageenan-induced acute inflammation in rats: the role of nitric oxide.

AbstractObjective: To investigate whether aminoguanidine (AG) treatment enhances the anti-inflammatory effect of diclofenac in an acute inflammation model in rats. Material and methods: In 48 rats carrageenan-induced paw edema was used as an acute inflammation model. Inflammatory activity was assessed at 1.5, 3 and 6 h after sub-planter injection of carrageenan (0.1 ml of a 1% solution in 0.85% saline). The anti-inflammatory effect of diclofenac (25 mg/kg, i.p.) was studied in comparison to that of the selective inducible nitric oxide synthase (iNOS) inhibitor, AG, and of nitric oxide donor, sodium nitroprusside (SNP). Results: AG, failed to inhibit inflammation during the first 3 h following carrageenan administration, but caused a slight, although statistically insignificant inhibition at 6 h. Diclofenac significantly reduced the carrageenan-induced edema in rat paw at all the time points studied. Administration of diclofenac after AG pretreatment caused significant (P < 0.001) reduction in edema that was double that of diclofenac alone 6 h after carrageenan injection. Administration of SNP as a single dose after AG pretreatment prevented any potentiation of anti-inflammatory response that was observed in the case of AG combined with diclofenac treatment. Conclusion: These results show that AG markedly potentiates the anti-inflammatory activity of diclofenac at 6 h and this potentiation effect is nitric oxide-dependent.

Inhibition of gastric mucosal damage by methylglyoxal pretreatment in rats.

The effect of methylglyoxal pretreatment on gastric mucosal injuries caused by 80% ethanol, 25% NaCl and 0.2 M NaOH, was investigated in rats. The effects caused by pylorous ligation accumulated gastric acid secretions and ethanol-induced changes in gastric mucus secretions, levels of proteins, nucleic acid, malondialdehyde (MDA) and non-protein sulfhydryl groups were also investigated. Methylglyoxal pretreatment at oral doses of 50, 100 and 200 mg/kg body weight was found to provide a dose-dependent protection against the ulcerogenic effects of different necrotizing agents used. With the same dose regimen methylglyoxal offered significant protection against ethanol-induced damage on the parameters evaluated for histopathology. Furthermore, the pretreatment afforded a dose-dependent inhibition of pylorous ligated accumulation of gastric acid secretions and ethanol-induced depletion of stomach wall mucus, proteins, nucleic acids, NP-SH contents and an increase in the MDA levels in gastric tissue. The protective effect of methylglyoxal against ethanol-induced damage to the gastric wall mucosa may be mediated through its effect on mucous production, proteins, nucleic acids, NP-SH groups and its free-radical scavenging property under the influence of polyamines stimulated by ornithine decarboxylase activity (ODC).

Effect of camel urine on the cytological and biochemical changes induced by cyclophosphamide in mice

Camel urine treatment was found to cause a significant cytotoxic effect in the bone marrow cells of mice. This cytotoxicity at higher doses was comparable with that of standard drug cyclophosphamide (CP). However, unlike CP, the camel urine treatment failed to induce any clastogenicity. The cytotoxicity induced by camel urine treatment was substantiated by the reduction of liver nucleic acids and glutathione levels and increased malondialdehyde (MDA) contents in the same animals. CP treatment was found to be highly clastogenic, cytotoxic and it reduced the levels of nucleic acids, proteins, glutathione and increased malondialdehyde concentration due to its prooxidant nature. The non-clastogenic nature of camel urine was attributed to the antioxidant and antimutagenic compounds present in camel urine. Pretreatment with camel urine increased the cytotoxicity of CP and intensified the CP induced reduction of liver nucleic acids, glutathione and increased the MDA concentration. The increase of CP induced cytotoxicity appears to be partly due to the additive effect of the two treatments on cellular lipid peroxidation.

Evaluation of the antiinflammatory activity of sodium valproate in rats and mice

1. Treatment of rats with sodium valproate (100, 200 and 400 mg/kg i.p.) reduced the paw oedema induced by carrageenan by 36, 15 and 48%, respectively, within 3 h . 2. The effect produced by the higher dose (400 mg/kg) was equivalent to that produced by indomethacin (100 mg/kg). At 100 and 400 mg/kg, sodium valproate decreased the granuloma formation by a significant level. Similar doses of sodium valproate did not affect the rectal temperature in yeast-fevered mice, except with a dose of 200 mg/kg, which showed a significant decrease at 180 and 240 min posttreatment. 3. In comparison, sodium salicylate reduced the hyperthermia very significantly throughout the study period. 4. In normothermic mice, the rectal temperature changed only with a 400 mg/kg dose, but did not respond to lower SV doses. 5. The results indicate that sodium valproate, useful clinically as an epileptic drug, may have a potential therapeutic use as a mild antiinflammatory agent.