Preventive and curative effect of methanolic extract of Gardenia gummifera Linn. f. on thioacetamide induced oxidative stress in rats

ObjectiveTo evaluate the antioxidant and antihepatotoxic effect of methanolic extract of Gardenia gummifera Linn. f. root (MEGG) on thioacetamide (TAA) induced oxidative stress in male Wistar rats.MethodsIn the preventive study, rats were administered with 125 and 250 mg/kg of MEGG for 9 days prior to TAA administration (100 mg/kg s.c.). In post-treatment groups, rats were treated with MEGG at doses of 125 and 250 mg/kg, 2, 24 and 48 h after TAA intoxication. Silymarin was used as a standard drug control (100 mg/kg). Hepatotoxicity was assessed by quantifying the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant potential of MEGG was evaluated by the estimation of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation [thiobarbituric acid reactive substances (TBARS)] in hepatic and renal tissues. Histopathological changes were also evaluated.ResultsMEGG significantly (P≤0.05) prevented the elevation of serum AST, ALT, ALP, LDH and tissue malondialdehyde levels in both experimental groups, when compared to the TAA alone treated groups. The rats receiving TAA plus MEGG exhibited significant (P≤0.05) increases in hepatic and renal antioxidant activities including GSH, GST, GR, GPx and CAT levels. Quantification of histopathological changes also supported the dose dependent protective effects of MEGG.ConclusionsThese observations suggest that MEGG has dose dependent hepatoprotective and antioxidant effect against TAA induced oxidative stress.     

Leukemic-like membrane properties acquired by B lymphocytes when depleted of 185,000-dalton macromolecular insoluble cold globulin

Human peripheral blood lymphocytes can be phenotypically identified by the presence of one or both of two proteins, 225,000-dalton macromolecular insoluble cold globulin (225-MICG) and 185,000-dalton MICG (185-MICG). T cells synthesize and insert into their plasma membrane 225-MICG, null cells 185-MICG, and B cells both 225 and 185- MICG. In contrast, the monoclonal B cells of chronic lymphocytic leukemia are characterized by the presence of 225-MICG and the absence of 185-MICG. We have recently found it possible to chemically deplete 185-MICG from viable normal B cells by treating them with diisopropylfluorophosphate (DFP), thus making normal B cells phenotypically resemble leukemic cells. In the present report we determined whether certain peculiar properties of these leukemic cells would be associated with the normal B cells chemically depleted of 185- MICG. In normal B cells, SIg diffuses in the lipid bilayer to form clusters and caps under appropriate conditions, while in chronic lymphocytic leukemia (CLL) cells this does not occur. Normal B cells depleted of 185-MICG fail to undergo capping of SIg or surface MICG under appropriate conditions. Both DFP-treated B cells and CLL cells tend to rupture when smeared on a glass slide. Both CLL cells and DFP- treated B cells fail to secrete 225-MICG after it has been synthesized intracellularly. The relationship of these findings to the mechanisms of secretion and capping are discussed.     

The spectrum of neurological manifestations and genotype–phenotype correlation in Indian children with Gaucher disease

Gaucher disease (GD), one of the most frequent autosomal recessive lysosomal storage disorders, occurs due to bi-allelic pathogenic variants in the GBA1. Worldwide, the c.1448T>C (L483P) homozygous pathogenic variant is reported to be associated with neurological GD phenotype. Clinical distinction between GD1 and GD3 may be challenging due to subtle neurological features. Objective methods to evaluate neurological signs and saccades may help in early diagnosis. This study was conducted to assess the neurological phenotype, and its severity using a modified severity scoring tool (mSST), and the genotype–phenotype correlation. A total of 45 children aged 2 years 6 months to 15 years with a confirmed enzymatic and molecular diagnosis of GD with or without therapy were recruited. mSST tool was used to assess the severity of the neurological phenotype. A digital eye movement tracker (View Point Tracker) was used to assess eye movements. Clinical and genetic findings were analyzed. Out of 45 patients, 39 (86.7%) had at least one neurological phenotype detected using the mSST tool, with impairment of cognitive function (68.8%, 31/45) being the commonest feature. Thirty-two of 45 (71%) were assessed for saccadic eye movements using the eye tracker. Of these, 62.5% (20/32) had absent saccades. Four children (8.9%, 4/32) without clinical oculomotor apraxia had absent saccades on the viewpoint eye tracker. Overall, 77.7% (35/45), had homozygosity for c.1448T>C in GBA1 of which 91.4% (32/35) had neurological manifestations. Other alleles associated with neurological phenotype included c.1603C>T(p.R535C), c.1184C>T (p.S395F), c.115+1G>A (g.4234G>A), c.260G>A (p.R87Q) and c.1352A>G (p.Y451C). To conclude, in India, the c.1448T>C pathogenic variant in GBA1 is the commonest  and is associated with neurological phenotype of GD. Therefore, every patient of GD should be assessed using the mSST scoring tool for an early pick up of neurological features. The routine use of a viewpoint eye tracker in children with GD would be useful for early recognition of saccadic abnormalities.