Devarakonda R. Krishna

Translocation and extra pulmonary toxicities of multi wall carbon nanotubes in rats

This study evaluated the ability of the multi wall carbon nanotubes (MWCNT) to induce extra pulmonary toxicities in rats following intra-tracheal (IT) instillation of two MWCNT. Two carbon nanoparticles were instilled into the lungs of rats (0.2, 1, and 5 mg/kg b.w.) and at different post-exposure intervals, blood and organs like liver, kidney, etc. were collected. The histopathological examination of liver tissues revealed a dose-dependent periportal lymphocytic infiltration, ballooning, foamy degeneration, and necrosis at all post-instillation periods. However, examination of kidney revealed the tubular necrosis and interstitial nephritis with 5 mg/kg dose at 1 month of post-instillation of both MWCNT. These liver and kidney toxicities were further confirmed by the elevated levels of respective tissue damage biomarkers. These results suggest the extra pulmonary toxicities of these carbon nanoparticles might be due to the translocation into the liver and kidney.

Antiinflammatory and antinociceptive activities of gossypin and procumbentin – cyclooxygenase‐2 (COX‐2) inhibition studies

In the present study the antiinflammatory and antinociceptive activities of a few selected flavonoids were investigated. Procumbentin, gossypin, chrysin and methylhespiridin were studied for antiinflammatory and antinociceptive activities using in vitro enzymatic assays and in animal models utilizing acetic acid‐induced writhing in mice and hind paw edema in rats. In vitro studies were performed using TMPD (NNN′N′‐tetramethyl‐p‐phenylene diamine) and oxygraphic methods for COX‐1 (cyclooxygenase‐1), COX‐2, 5‐LOX (5‐lipoxygenase) and 15‐LOX. Gossypin and procumbentin showed COX‐2 inhibitory activity and exhibited IC50 (COX‐2/COX‐1) ratios of 0.14 and 0.11, respectively. None of the flavonoids tested in this study showed LOX inhibitory activity. Four groups were studied for each test compound following intraperitoneal (i.p.) administration of doses of 10, 30 and 100 mg/kg. Antiinflammatory activity was measured by the carrageenin‐induced rat hind paw edema model and antinociceptive activity by acetic acid‐induced writhing. Procumbentin and gossypin showed antinociceptive activity at the 100 mg/kg dose. Gossypin showed antiinflammatory activity at doses of 10, 30, 100 mg/kg. Procumbentin and gossypin exhibited COX‐2 inhibitory activity when tested by in vitro methods. Procumbentin and gossypin showed antinociceptive, and gossypin showed antiinflammatory, activities. Copyright

Cytotoxic activity of a flavanone from the stem of Bauhinia variegata Linn

A flavanone has been isolated first time from the stem of Bauhinia variegata, and its structure was identified by colour reactions and spectral analysis. In a search for novel anticancer compounds from medicinal plants, the isolated flavanone was tested for cytotoxic activity against 57 human tumour lines, representing leukaemia, non-small cell lung, colon, central nervous system, melanoma, ovarian, renal, prostate and breast cancers. The results showed that the flavanone has cytotoxic activity against human tumour cell lines.

In vitro cytotoxicity of multi-wall carbon nanotubes on human cell lines

The aim of this study was to evaluate the in vitro toxicity of two multi-wall carbon nanotubes on four different cell lines: human alveolar epithelial (A549) cells, hepatocytes (Hep 3B cells), human embryonic kidney cells, and intestinal (P407 cells) cells. The adverse effects of carbon nanoparticles were analyzed after 24 h incubation with different cell lines using the trypan blue dye exclusion method. Incubation of carbon nanotubes with different cells produced a concentration-dependent inhibition of growth of the cells. The TC50 or IC50 values (toxic concentration 50, i.e., concentration of particles inducing 50% cell mortality) of two nanoparticles were (1) found to be in the range 23.5–30.5 µg mL−1, and (2) less than that of quartz (known toxic agent, 28.8–66.9 µg mL−1), indicating the greater cytotoxic effect of carbon nanoparticles than quartz particles.

Influence of Rifampicin Pretreatment on the Pharmacokinetics of Tinidazole in Healthy Male Volunteers

ObjectiveTo investigate the effect of pretreatment with rifampicin (rifampin) on the pharmacokinetics of tinidazole in healthy male volunteers.DesignBefore/after non-blinded investigation conducted in healthy volunteers.Study Participants12 healthy male volunteers with a mean age of 24 ± 3 years.MethodsAfter an overnight fast, tinidazole (500mg tablet) was administered to the volunteers, either alone or after a 5-day pretreatment period with a once-daily dose of rifampicin 600mg (2 × 300mg capsules) under direct observation. Serum concentrations of tinidazole were measured by reverse-phase high performance liquid chromatography Pharmacokinetic parameters were determined from noncompartmental model analysis using the computer program RAMKIN.ResultsA significant difference was observed in area under the concentration-time curve (AUC) from 0 to 48 hours (254.77 ± 31.46 vs 208.07 ± 25.57 mg/h/L, p < 0.0001), AUC from 0 to infinity (299.86 ± 47.70 vs 231.54 ± 36.19 mg/h/L, p < 0.0001], elimination half-life (16.98 ± 2.73 vs 13.93 ± 3.45h, p < 0.0018) and clearance (27.62 ± 3.61 vs 35.82 ± 4.95 ml/h/kg, p < 0.0001) of tinidazole administered before and after rifampicin pretreatment. However, peak concentration (Cmax), time to reach Cmax and apparent volume of distribution were not affected significantly.ConclusionsRifampicin pretreatment reduced the AUC of tinidazole by 23% and increased the clearance by 29%. This may be due to increased metabolism of tinidazole as a result of the induction of cytochrome P450 2C9 and 3A4 in liver/intestine and/or P-glycoprotein-mediated exsorption into the intestines. This interaction, however, may not have significant clinical relevance and does not warrant dosage adjustment because the extent of alteration in bioavailability of tinidazole is less than 25%.