Mechanism Of Nephroprotection By Picrorhiza Kurroa.

BACKGROUND: Humans are exposed either deliberately or unintentionally to a variety of diverse chemicals that harm the kidney. To reduce the alarming high incidence of nephrotoxicity, some chemical as well as herbal alternatives are needed. Nimesulide belongs to a group of antiinflammatory drugs that are in common use in our society. Like all non-steroidal antiinflammatory drugs, it carries a potential threat of nephrotoxicity especially when other risk factors are present in user. The objective of this study was to find herbal alternative with antiinflammatory and nephroprotective qualities and to bring into light its mechanism of nephroprotection. METHODS: This experimental study was conducted on mice at National Institute of Health, Islamabad from Feb 2013 to March 2014. Nimesulide was given in a dosage of 750 mg/kg body weight for 3 days to induce nephrotoxicity and protective effect of Picrorhiza kurroa was noted in two doses of 250 mg/kg and 500 mg/kg for 14 days. Renal function tests were done and urinary PGE2 was measured to assess the effect of nimesulide and Pk on kidneys. RESULTS: In our study, significant improvement was seen in serum urea and creatinine levels in mice receiving low and high dose Picrorhiza kurroa. However, no significant improvement was noted in urinary PGE2 showing that the mechanism of nephroprotection is not by vasodilatory effect of Pk. CONCLUSIONS: This study showed nimesulide nephrotoxic potential and Pk is a good herbal antiinflammatory and nephroprotective alternative for nimesulide but its mechanism of nephroprotection is not by PGE2.

Proteomic identification of human urinary biomarkers in diabetes mellitus type 2.

BACKGROUND: During the proteomic era, one of the most rapidly growing areas in biomedical research is biomarker discovery, particularly using proteomic technologies. The urinary proteome is known to be a valuable field of study and has become one of the most attractive subdisciplines in clinical proteomics for human diseases. We have described the levels of protein biomarkers specific to diabetes mellitus type 2 in the Pakistani population using proteomic technology. METHODS: One hundred type 2 diabetes patients with 50 age- and sex-matched normal healthy controls were recruited from Sheikh Zayed Hospital, Lahore, Pakistan. Urinary proteins were analyzed by two-dimensional liquid chromatography, using chromatofocusing in the first dimension and reverse-phase chromatography in the second, followed by mass spectrometric analysis. Levels of the proteins, which were found to vary in the diabetes type 2 patients compared to the controls, were then determined by enzyme-linked immunosorbent assay in all the samples. RESULTS: Levels of transthyretin, α-1-microglobulin/bikunin precursor, and haptoglobin precursor decreased by 30.8%, 55.2%, and 81.45%, whereas levels of albumin, zinc α2 glycoprotein, retinol binding protein 4, and E-cadherin increased by 486.5%, 29.23%, 100%, and 693%, respectively, in the diabetes patients compared to the controls. CONCLUSIONS: Variation in the levels of these identified protein biomarkers have been reported in other pathological states. Assessment of the levels of these biomarkers will be helpful not only in early diagnosis but also in prognosis of diabetes mellitus type 2.

Proteomic identification of human serum biomarkers in diabetes mellitus type 2.

Discovery of protein biomarkers in different diseases is an important area of research in the field of proteomics. We have described the levels of protein biomarkers specific to diabetes mellitus type 2 in the local population of Pakistan using proteomic technology. Type 2 diabetic patients, age and sex-matched normal healthy controls were recruited from Sheikh Zayed Hospital, Lahore, Pakistan. Plasma proteins were analysed by 2D liquid chromatographic system in which samples were initially fractionated by chromatofocusing and the selected fractions were further analysed by reverse-phase high performance liquid chromatography. The proteins which showed variation between test and control samples were identified by MALDI-TOF analysis. All the samples belonging to the control and diabetic groups were then analyzed by ELISA and estimated four proteins which were found to vary. Levels of apolipoprotein A-I was found to decrease by -6.4% while apolipoprotein E, leptin and C reactive protein (CRP) were increased by +802, +842 and +872%, respectively, in the diabetic patients as compared to the controls. The discovery of these marker proteins might thus provide an adjunctive method for early detection of risk for this disease.