Synthesis and antioxidant activity of quinolinobenzothiazinones.

A new series of structurally diverse quinolinobenzothiazinones has been synthesized with the annulation of heterocyclic structural pharmacophores. The synthesized quinolinobenzothiazinones have been evaluated for their antioxidant (LPO & GSH) and radical scavenging activities (DPPH and ABTS assays).

Protective effects of Mentha piperita Linn on benzo[a]pyrene-induced lung carcinogenicity and mutagenicity in Swiss albino mice.

The chemopreventive and antimutagenic effects of an aqueous extract of Mentha piperita leaves were evaluated by using 9 week medium term model of benzo[a]pyrene (BP)-induced lung tumors. Lung tumors were induced by a single subcutaneous injection in the scapular region with BP in newborn Swiss albino mice (<24 h old). The oral administration of Mentha extract (ME) showed a significant reduction in the number of lung tumors from an incidence of 67.92% in animals given only BP to 26.31%. The inhibition rate was 61.26% in ME treated group with respect to reference group (BP-alone). However, tumor multiplicity was reduced from 0.83 in the BP-alone group to 0.31 in the BP+ME group. Also, ME treatment reduced the frequency of BP-induced chromosomal aberrations and micronuclei in bone marrow cells and decreased the levels of lipoperoxides and increased sulfhydryl groups in liver as well as lung. In cell-free assays, ME showed strong scavenging activity for both the DPPH* and ABTS*+ radicals. ME had an IC50 value of 272 microg/ml in the DPPH* assay. The chemopreventive action and antimutagenic effects observed in the present study is attributed to the antioxidative and radical scavenging properties of ME.

Modulatory effects of Mentha piperita on lung tumor incidence, genotoxicity, and oxidative stress in benzo[a]pyrene-treated Swiss albino mice.

Mentha piperita or peppermint is currently used for alleviating nausea, flatulence, and vomiting. In the present investigation, we evaluated the chemopreventive, antigenotoxic, and antioxidative effects of an aqueous extract of Mentha piperita leaves. One-day-old Swiss albino mice were treated with a single subcutaneous injection of 0.5 mg benzo[a]pyrene (BP) and then given either water or a Mentha extract (ME; 1 g/kg body weight) by gavage starting at 3 weeks of age (weaning). The mice were killed at 9 weeks of age and tested for lung tumor incidence (chemoprevention); bone marrow micronucleus and chromosome aberration frequency (antigenotoxicity); and levels of liver and lung sulfhydral groups, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation (LPO) (antioxidative properties). The ME treatment resulted in a significant reduction in the number of lung adenomas from an incidence of 67.92% in animals given only BP to 26.31%, an inhibition of 61.26%. Tumor multiplicity was 1.22 in the BP-alone group and 1.15 in the BP + ME group. In addition, compared with the animals in the BP-alone group, ME reduced the frequency of chromosomal aberrations and micronuclei in bone marrow cells and decreased the levels of LPO and increased reduced glutathione content, and SOD and CAT activities in liver as well as lung. The results of this study indicate that ME is chemopreventive and antigenotoxic when given subsequent to an initiating dose of BP in newborn Swiss albino mice. The chemopreventive action and antigenotoxic effects observed in the present study may be due to the antioxidative properties of ME.

Antioxidative effect of Rajgira leaf extract in liver of Swiss albino mice after exposure to different doses of gamma radiation.

The radioprotective effect of Rajgira leaf extract (800 mg/kg b.wt.) was studied in the liver of Swiss albino mice at various post-irradiation intervals between day 1 and 30 after its oral administration for 15 consecutive days prior to whole body gamma irradiation with 6, 8 and 10 Gy of gamma rays. In this study, abnormal and binucleated hepatocytes were counted in both the control and experimental sets because these hepatocytes are good indicators of radiation-induced damage. In the experimental (RLE + irradiation) sets, the percentage of abnormal and binucleated hepatocytes was lower compared with their respective control (irradiation alone) sets at each autopsy interval with all three radiation doses studied. The increase in the percentage of these hepatocytes was also found to be dose-dependent in the control as well as in the RLE treated (experimental) sets. Thus, Rajgira leaf extract (RLE) treatment given before irradiation protects mouse liver against radiation-induced lesions by increasing the GSH content and decreasing the LPO level.

Modulatory influence of Adhatoda vasica Nees leaf extract against gamma irradiation in Swiss albino mice.

The radiomodulatory influence of ethanolic extract of Adhatoda vasica Nees leaf extract against radiation-induced hematological alterations in peripheral blood of Swiss albino mice was studied at various post-irradiation intervals between 6 h to 30 days. Oral administration of A. vasica leaf extract (800 mg/kg body weight) prior to whole body irradiation showed a significant protection in terms of survival percentage and hematological parameters. Mice exposed to radiation (8.0 Gy) without A. vasica leaf extract pre-treatment exhibited signs of radiation sickness like anorexia, lethargicity, ruffled hairs and diarrhoea and such animals died within 25 days post-irradiation. The dose reduction factor (DRF = 1.6) for A. vasica leaf extract was calculated from LD50/30 values. A significant decline in hematological constituents (RBCs, WBCs, Hb and Hct) was evident till day 15 and no animal could survive beyond day 25. Conversely, animals pre-treated with A. vasica leaf extract showed 81.25% survival till 30 days after exposure and a gradual recovery was noted in the hematological values. However, these hematological values remained significantly below the normal even till day 30. A significant decrease in blood reduced glutathione (GSH) content and increase in lipid peroxidation (LPO) level was observed in control animals (Radiation alone). However, A. vasica leaf extract pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level. A significant increase in the serum alkaline phosphatase activity and decrease in acid phosphatase activity was observed in A. vasica leaf extract pretreated irradiated animals during the entire period of study.

Protection of swiss albino mice against whole-body gamma irradiation by Mentha piperita (Linn.).

The radioprotective effects of Mentha oil (Mentha piperita Linn.) against radiation induced haematological alterations in peripheral blood and the survival of Swiss albino mice were studied. Mentha oil 40 micro L/animal/day for 3 consecutive days when fed orally prior to whole-body gamma irradiation (8 Gy) showed protection of the animals in terms of the survival percentage and haematological parameters in mice. Fifty per cent of the animals died within 20 days and 100% mortality was observed up to 30 days post-irradiation in the control irradiated group. Whereas only 17% of the mice died within 30 days in the experimental group (Mentha oil pretreated irradiated). The total RBC count decreased maximally at 24 h (3.45 +/- 0.20 x 10(12)/L, p < 0.001), similar observations were obtained for the WBC count, haemoglobin content and haematocrit percentage in the irradiated control animals. However, in irradiated animals pretreated with Mentha oil, although the initial values of haematological components were lower they later showed a remarkable recovery reaching normal at 30 days post-irradiation compared with the irradiated control animals. In general, the recovery of the blood cell number in irradiated animals depends on the survival of stem cells and their derivatives. The results from the present study suggest that the oil of Mentha piperita (Linn.) has a radioprotective role in stimulating/protecting the haematopoietic system. Hence, enhanced survival and an increase in the haematological constituents of peripheral blood of mice against lethal gamma radiation was observed.

Radiomodulatory influence of Rajgira (Amaranthus paniculatus) leaf extract in Swiss albino mice.

Radiomodulatory effect of Rajgira leaf extract against 6, 8 and 10 Gy gamma radiation has been evaluated by 30 day survival of Swiss albino mice. Animals of control groups (untreated irradiated) showed diarrhoea, ruffled hairs, epilation, facial edema and consistent decrease in body weight. These signs were less severe/absent in experimental groups (Rajgira treated irradiated), and recovery in body weight was also early and faster. Thirty day survivability was 66 per cent in control group, exposed to 6 Gy, whereas no animal survived beyond 14 and 10 days after irradiation with 8 and 10 Gy gamma rays respectively. However, 100, 60 and 25 percent survivability was observed in experimental groups at 6, 8 and 10 Gy respectively. Regression analysis of survival data showed that the LD50/30 values were 6.33 and 8.62 Gy for control and experimental animals respectively. The dose reduction factor (DRF) was computed as 1.36. A significant decrease in GSH content and increase in LPO level was observed in control animals, whereas in Rajgira pretreated irradiated animals the level of GSH was recorded significantly higher but LPO level decreased significantly. The results from the present study suggest that Rajgira pretreatment provide protection against gamma irradiation in mice.

Radioprotection of Swiss albino mice by plant extract Mentha piperita (Linn.).

The oral administration of Mentha extract (ME) before exposure to gamma radiation was found to be effective in increasing the frequency of radiation-induced endogenous spleen colonies. A significant increase in the weight of the spleen was observed in animals of the Mentha and radiation combined group in comparison to the irradiation-alone group on day 10 of postirradiation. Furthermore, a significant increase in the body weight of animals in the Mentha and radiation combined group was observed in all the radiation doses studied. A regression analysis of survival data yielded LD50/30 as 6.48 +/- 0.07 and 11.59 +/- 0.21 Gy for the irradiation-alone and the Mentha and radiation combined group, respectively, and produced a dose reduction factor (DRF) of 1.78. Significant increases in total erythrocyte and leucocyte counts, hemoglobin concentration, and hematocrit values were observed in the animals of the Mentha and radiation combined group in comparison to the hematological values observed in the irradiation-alone group at all radiation doses studied (6, 8, and 10 Gy). A dose-dependent decrease in reduced glutathione (GSH) content and an increase in lipid peroxidation (LPO) levels were observed in control animals. However, the animals of the Mentha and radiation combined group exhibited a significant increase in GSH content and a decrease in LPO level, but the values remained below normal. A significant increase in the serum alkaline phosphatase activity was observed in the animals of the Mentha and radiation combined group during the entire period of study, and normal range was evident at 24 h (6 Gy) and day 5 (8 Gy). However, this level could not be restored even at day 30 in 10 Gy exposed animals. Measured acid phosphatase activity in the animals of the Mentha and radiation combined group was found to be significantly lower than the respective controls and attained normal value at day 5 (6 and 8 Gy) and day 20 (10 Gy).

Mentha piperita (Linn.) leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice.

Oral administration of M. piperita (1 g/kg body weight/day) before exposure to gamma radiation was found to be effective in protecting against the chromosomal damage in bone marrow of Swiss albino mice. Animals exposed to 8 Gy gamma radiation showed chromosomal aberrations in the form of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges and acentric fragments. There was a significant increase in the frequency of aberrant cells at 6 hr after irradiation. Maximum aberrant cells were observed at 12 hr post-irradiation autopsy time. Further, the frequency of aberrant cells showed decline at late post-irradiation autopsy time. However, in the animals pretreated with Mentha extract, there was a significant decrease in the frequency of aberrant cells as compared to the irradiated control. Also significant increase in percentage of chromatid breaks, chromosome breaks, centric rings, dicentrics, exchanges, acentric fragments, total aberrations and aberrations/damaged cell was observed at 12 hr post-irradiation autopsy time in control animals, whereas Mentha pretreated irradiated animals showed a significant decrease in percentage of such aberrations. A significant decrease in GSH content and increase in LPO level was observed in control animals, whereas Mentha pretreated irradiated animals exhibited a significant increase in GSH content and decrease in LPO level but the values remained below the normal. The radioprotective effect of Mentha was also demonstrated by determining the LD(50/30) values (DRF = 1.78). The results from the present study suggest that Mentha pretreatment provides protection against radiation induced chromosomal damage in bone marrow of Swiss albino mice.

Modulation of serum phosphatases activity in Swiss albino mice against gamma irradiation by Mentha piperita Linn.

The modulatory influence of mentha oil (Mentha piperita Linn.) against a lethal dose (8.0 Gy) of gamma irradiation on the activities of serum phosphatases in Swiss albino mice was studied at various post-irradiation intervals between 6 h and 30 days. Mentha oil (40 microL/animal/day) given orally for 3 consecutive days prior to whole-body irradiation (8.0 Gy) showed a modulation of activity of serum phosphatases. The values of acid phosphatase activities were significantly higher in the irradiated groups throughout the experiment compared with the mentha treated unirradiated animals. However, the acid phosphatase activity of mentha treated irradiated animals showed a significant decline over untreated irradiated animals at all autopsy intervals, which attained the normal value on day 5. On the contrary, a marked decrease in serum alkaline phosphatase activity was noted in both irradiated groups but in the mentha treated irradiated group the values of alkaline phosphatase activity were found to be significantly higher than the respective control during the period of study being normal at day 5 post-irradiation and onwards.

Mentha piperita (Linn) leaf extract provides protection against radiation induced alterations in intestinal mucosa of Swiss albino mice.

Intestinal protection in mice against radiation injury by M. piperita (1 g/kg body weight/day) was studied from day 1 to day 20 after whole body gamma irradiation (8 Gy). Villus height, goblet cells/villus section, total cells, mitotic cells and dead cells/crypt section in the jejunum are good parameters for the assessment of radiation damage. There was significant decrease in the villus height, number of total cells and mitotic cells/crypt section, whereas goblet cells and dead cells showed significant increase after irradiation. Mentha pretreatment resulted in a significant increase in villus height, total cells and mitotic cells, whereas goblet cells and dead cells showed a significant decrease from respective irradiated controls at each autopsy day. The results suggest that Mentha pretreatment provides protection against radiation induced alterations in intestinal mucosa of Swiss albino mice.

Modulatory effect of Mentha piperita (Linn.) on serum phosphatases activity in Swiss albino mice against gamma irradiation.

Mentha extract (ME; 1 g/kg body wt) given orally for three consecutive days prior to whole body irradiation (8 Gy) showed modulation of activity of serum phosphatases in albino mice. Values of acid phosphatase activities were significantly higher in untreated irradiated group throughout the experiment. Irradiated animals pretreated with ME showed significant decline in acid phosphatase activity as compared to untreated irradiated animals at all autopsy intervals and attained normalcy at day 5. A marked decrease in serum alkaline phosphatase activity was recorded in both irradiated groups. However, in ME pretreated irradiated group, values of alkaline phosphatase activity remained significantly higher than untreated irradiated animals at all intervals and attained normalcy from day 5 onwards.