Pilea umbrosa ameliorate CCl induced hepatic injuries by regulating endoplasmic reticulum stress, pro-inflammatory and fibrosis genes in rat

BACKGROUND@#Pilea umbrosa (Urticaceae) is used by local communities (district Abbotabad) for liver disorders, as anticancer, in rheumatism and in skin disorders.@*METHODS@#Methanol extract of P. umbrosa (PUM) was investigated for the presence of polyphenolic constituents by HPLC-DAD analysis. PUM (150 mg/kg and 300 mg/kg) was administered on alternate days for eight weeks in rats exposed with carbon tetrachloride (CCl). Serum analysis was performed for liver function tests while in liver tissues level of antioxidant enzymes and biochemical markers were also studied. In addition, semi quantitative estimation of antioxidant genes, endoplasmic reticulum (ER) induced stress markers, pro-inflammatory cytokines and fibrosis related genes were carried out on liver tissues by RT-PCR analysis. Liver tissues were also studied for histopathological injuries.@*RESULTS@#Level of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and glutathione (GSH) decreased (p < 0.05) whereas level of thiobarbituric acid reactive substance (TBARS), HO and nitrite increased in liver tissues of CCl treated rat. Likewise increase in the level of serum markers; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin was observed. Moreover, CCl caused many fold increase in expression of ER stress markers; glucose regulated protein (GRP-78), x-box binding protein1-total (XBP-1 t), x-box binding protein1-unspliced (XBP-1 u) and x-box binding protein1-spliced (XBP-1 s). The level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) was aggregated whereas suppressed the level of antioxidant enzymes; γ-glutamylcysteine ligase (GCLC), protein disulfide isomerase (PDI) and nuclear erythroid 2 p45-related factor 2 (Nrf-2). Additionally, level of fibrosis markers; transforming growth factor-β (TGF-β), Smad-3 and collagen type 1 (Col1-α) increased with CCl induced liver toxicity. Histopathological scrutiny depicted damaged liver cells, neutrophils infiltration and dilated sinusoids in CCl intoxicated rats. PUM was enriched with rutin, catechin, caffeic acid and apigenin as evidenced by HPLC analysis. Simultaneous administration of PUM and CCl in rats retrieved the normal expression of these markers and prevented hepatic injuries.@*CONCLUSION@#Collectively these results suggest that PUM constituted of strong antioxidant chemicals and could be a potential therapeutic agent for stress related liver disorders.

Frequency and clinical Importance of Anti - TG auto antibodies [ATG]

To note the frequency of anti thyroglobulin autoantibodies [ATG] and its clinical importance in 25 follow-up cases of differentiated thyroid cancer [DTC]. Design: A case control study. Place and Duration of Study: The total duration of study was one year [September 2000 to August 2001]. Majority of the patients included were the routine follow-up cases at IRNUM, Peshawar. However, few of the cases were also included from NORI, Islamabad and AFIP, Rawalpindi. Subjects and All the patients who had undergone sub-total or total thyroidectomy followed by I-131 ablation therapy were selected for this study. Thyroglobulin [Tg] and ATG were measured using immunometric assay technique with reference range of non-detectable to 40 IU/L. Patients with serum Tg level ' 10 ng/mL were included in group-1 [n=15] and all the remaining [n=10] in group-2. Overall, 11 patients showed ATG titer above the pre-defined threshold level. In group -1 patients, 8 had positive anti-Tg antibodies in their sera while in group-2, it was positive in only 3 cases. Risk of relapsing metastatic/recurrent disease in association with ATG was calculated which showed that patients with positive ATG have almost seven - fold increased risk of having recurrent/metastatic disease than those who do not. Samples for s-Tg measurements must also be evaluated for ATG status because more than one-third of these patients have positive ATG titer in their sera. Although in the presence of positive ATG, the risk of concurrent metastatic/recurrent thyroid disease is increased but still more studies are required to support its significance