The potential protective influence of flaxseed oil against renal toxicity induced by thioacetamide in rats

The present study was aimed to evaluate the influence of flaxseed oil on renal toxicity induced by thioacetamide in male rats. The animals were distributed into four groups. Rats of the first group were served as control. Rats of the second group were exposed to thioacetamide. Rats of the third group were treated with flaxseed oil and thioacetamide. Rats of the fourth group were treated with flaxseed oil. Significant increases of blood creatinine and uric acid were observed in TAA-treated rats after three weeks. In thioacetamide group, the levels of serum creatinine, blood urea nitrogen and uric acid were significantly elevated after six weeks. Histopathologically, the renal sections from thioacetamide-treated rats showed severe alterations in the structure of renal corpuscles including a degeneration of glomeruli and Bowman’s capsules. Administration of flaxseed oil protects the observed biochemical and histopathological alterations induced by thioacetamide exposure. Hence, the results of this study suggest that flaxseed oil protects against thioacetamide-induced renal injury and the protective influence of flaxseed oil may be attributed to its antioxidant role.     

Leucas pachmarhiensis sp. nov. (Lamioideae; Lamiaceae) from central India

A new species, Leucas pachmarhiensis (Lamiaceae), is described and illustrated from the Pachmarhi Biosphere Reserve, Hoshangabad district, Madhya Pradesh, India with conservation status assessed as ‘Critically Endangered’. This novelity is endemic to central India and belongs to Leucas sect. Plagiostoma. It differs from other species of this section by its height up to 120 cm, and inflorescence positioned at multiple nodes. Detailed notes on its conservation status and ecology are provided.     

Gamma radiation and interspecific hybridization in jute ( Corchorus capsularis L. and C. olitorius L.)

Although numerous attempts have been made during the last five decades, no hybrids combining the qualities of the two commercially most important species have been released so far. Dry seeds of Corchorus capsularis L. var. D-154 and Corchorus olitorius L. var. C.G. were irradiated with gamma rays of various intensities from 70 Kr. to 100 Kr. and were sown in the field. Abnormal plants of the first generation showing bilobed and crinkled characters in their leaves induced by gamma rays were chosen as male parents. 300 crosses of different combinations were made. In all 120 fruits developed into maturity. All the seeds failed to germinate except those from the crosses ♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) and ♀ D-154 (0 Kr.) × ♂ C.G. (70 Kr.). F₁ plants from the cross ♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) inherited the bilobed character of the male parent whereas the plants from the other cross failed to show any sign of inheritance of the male parent. This indicated that the plants from the cross ♀ C.G. (0 Kr.) × ♂ D-154 (80 Kr.) were hybrids. These hybrids attained a greater height than the controls and were highly fertile.     

Factors involved in the maintenance of luteal function in the pseudopregnant rat

Some data on a new antispermatogenic and antifertility compound, DL-6-(N-alpha-pipecolinomethyl)-5-hydroxy-indane maleate (PMHI) are presented. It was found that PMHI depressed testicular weight and interfered with spermatogenesis and fertility in the male rat. At equal doses, by weight, PMHI caused a greater reduction in testicular weight than WIN 18446, nitrofurazone, methallibure, and diethylstilbestrol, but lesser reductions in seminal vesicle and ventral prostate weights than were obtained with the 2 antigonadotropic compounds, methallibure and diethylstilbestrol. The data obtained in the experiments indicate that administration of PMHI causes sterility in male rats as a consequence of antispermatogenic activity. At low dosage levels (3 mg/kg), the action was reversible, but animals given 6.25 mg/kg/day or more remained sterile for 19 weeks following the treatment period. Doses of the compound which were effective in the male rat did not interfere with normal estrous cycles or fertility when administered to female rats.     

Kinetics and Molecular Docking Study of an Anti-diabetic Drug Glimepiride as Acetylcholinesterase Inhibitor: Implication for Alzheimer’s Disease-Diabetes Dual Therapy

Neurochemical Research - At the present time, treatment of two most common degenerative disorders of elderly population i.e., Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease (AD) is a...     

Glycated phosphatidylethanolamine promotes macrophage uptake of low density lipoprotein and accumulation of cholesteryl esters and triacylglycerols.

Non-enzymatic glycation of low density lipoprotein (LDL) has been suggested to be responsible for the increase in susceptibility to atherogenesis of diabetic individuals. Although the association of lipid glycation with this process has been investigated, the effect of specific lipid glycation products on LDL metabolism has not been addressed. This study reports that glucosylated phosphatidylethanolamine (Glc-PtdEtn), the major LDL lipid glycation product, promotes LDL uptake and cholesteryl ester (CE) and triacylglycerol (TG) accumulation by THP-1 macrophages. Incubation of THP-1 macrophages at a concentration of 100 micrograms/ml protein LDL specifically enriched (10 nmol/mg LDL protein) with synthetically prepared Glc-PtdEtn resulted in a significant increase in CE and TG accumulation when compared with LDL enriched in non-glucosylated PtdEtn. After a 24-h incubation with LDL containing Glc-PtdEtn, the macrophages contained 2-fold higher CE (10.11 +/- 1.54 micrograms/mg cell protein) and TG (285.32 +/- 4.38 micrograms/mg cell protein) compared with LDL specifically enriched in non-glucosylated PtdEtn (CE, 3.97 +/- 0.95, p < 0.01 and TG, 185.57 +/- 3.58 micrograms/mg cell protein, p < 0.01). The corresponding values obtained with LDL containing glycated protein and lipid were similar to those of LDL containing Glc-PtdEtn (CE, 11.9 +/- 1.35 and TG, 280.78 +/- 3.98 micrograms/mg cell protein). The accumulation of both neutral lipids was further significantly increased by incubating the macrophages with Glc-PtdEtn LDL exposed to copper oxidation. By utilizing the fluorescent probe, 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate (DiI), a 1.6-fold increase was seen in Glc-PtdEtn + LDL uptake when compared with control LDL. Competition studies revealed that acetylated LDL is not a good competitor for DiI Glc-PtdEtn LDL (5-6% inhibition), whereas glycated LDL gave an 80% inhibition, and LDL + Glc-PtdEtn gave 93% inhibition of uptake by macrophages. These results indicate that glucosylation of PtdEtn in LDL accounts for the entire effect of LDL glycation on macrophage uptake and CE and TG accumulation and, therefore, the increased atherogenic potential of LDL in hyperglycemia.     

Tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives as microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors: SAR and in vivo efficacy in hyperalgesia pain model

A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE₂ release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity. Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic stability in liver microsomes, high plasma protein binding (PPB) and no significant inhibition observed in clinically relevant CYP isoforms. Besides, selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic profile and oral bioavailability (%F = 33 and 85). Additionally, the representative mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS-induced thermal hyperalgesia guinea pig pain model.     

Specific 50'CpG island methylation signatures of FHIT and p16 genes and their potential diagnostic relevance in Indian breast cancer patients

Even after tremendous molecular studies, early detection,more accurate and sensitive diagnosis, and prognosis of breast cancer appear to be a riddle so far. To stab the enigma, this study is designed to envisage DNA methylation signatures as cancer-specific and stage-specific biomarkers in Indian patients. Rigorous review of scattered scientific reports on aberrant DNA methylation helped us to select and analyze a potential tumor suppressor gene pair (FHIT and p16 genes) in breast cancer patients. Methylation signatures from 232 primary sporadic breast cancer patients were pinpointed by methylation-specific PCR (MSP). To increase the sensitivity, we combined both MSP and expression studies (RT-PCR and Northern blotting) in a reproducible manner. Statistical analysis illustrated that hypermethylation of FHIT gene ( p < 0.0001) and p16 gene ( p=0.04) may be used as a potential diagnostic marker to diagnose the early and locally advanced stages of breast cancer. Additionally, the study authenticates the dependency of methylation and expressional loss of p16 gene on FHIT gene silencing. This observation not only describes the severity of disease when both genes are silenced but also drives to speculate the molecular cross talk between two genes or genetic pathways dictated by them separately.