No abstract

Hepatotoxicity is a term used to describe serious health complications of liver disease caused by a variety of factors. Nuclear factor erythroid-2 linked factor (Nrf2) as a potential mediator of hepatotoxicity via inflammatory and induction of oxidative stress, oxidation produces more toxic compounds caused more pathogenic cases; therefore, to maintain sufficient homeostasis, involve antioxidant materials and detoxification factors. Controlling cytokine activity in normal cells is a useful way to regulate the signaling pathway of Nrf2. Recent studies found a relation between each Nrf2 and NF-κB activation and drug-induced liver injury.  This review presents a detailed and conformation update of Nrf2 roles in hepatotoxicity which considers that drug-induced liver injury is the main problem to draw attention in medical clinics and to develop new drugs with less harmful to the liver. In addition to that. Kept each of normal oxidation and cytokines levels is crucial responses for cells alteration and remaining to survive.

Podocyte injury represents the main reason for proteinuria and renal disease in diabetic and non-diabetic patients. Recently Liraglutide as a GLP-1 analog is hypothesized to play a vital role in preventing kidney damage by antiinflammatory and anti-apoptotic effect mechanisms. This study was established to evaluate the effect of Liraglutide on deterioration that happens with time in chronic kidney disease. 36 male Wister rats with a weight of 250-300 g were used in this study. All selected animals were examined and determined to be normal on general examination. Rats were divided into three groups (12rats/group): control group: negative control group injected normal saline I.P, induction group: single I.P dose (7.5 mg/kg) of doxorubicin for 14 days then administered 0.5ml/kg normal saline intraperitoneal for 28 days, and treatment group: single I.P dose (7.5 mg/kg) of doxorubicin for 14 days then administered I.P Liraglutide 200μg/kg/day freshly dissolve in 0.5ml /kg normal saline 28 days. The treatment group appeared significantly decreased (P< 0.05) in the pro-inflammatory expression of TNF-α as compared with the induction group, while the treatment group revealed a significant increased (P< 0.05) in the expression of anti-apoptotic BCL-2 in the proximal tubule of the kidney. Besides the effect of Liraglutide on renal deterioration by lowering blood glucose, the main causes of oxidative stress, Liraglutide as GLP-1 analog can reduce the consequence of proteinuria in the cases of glomerulosclerosis and tubulointerstitial damage by decreased pro-inflammatory TNF-α expression and increase expression of BCL-2 in that cell.

Podocyte injury is a major factor in many renal diseases leading to proteinuria that causes the risk of developing kidney deterioration. Glomerulosclerosis and tubulointerstitial fibrosis are the main histopathological feature as consequence of inflammation and apoptosis a result of   long period of tubular protein load. Liraglutide an incretin hormone (GLP-1) analogue has effective as glycemic control in patient with type 2 diabetes. In recent years, liraglutide appear protected mechanism against inflammation and apoptosis for many tissues through GLP-1 receptor (GLP-1R) activation unrelated with glycemic control.  36 animal Wister rats used in this experiment, first group include 12 rats set as control group received just the normal saline, while second group include 24 rats induced podocyte injury by doxorubicin single dose and third group treated either normal saline or liraglutide (200 µg /kg/day I.P) for 28 days.  Histopathological study is used to assess the protected effect of liraglutide on podocyte injury induced in male rats through three main histopathological changes (glomerulosclerosis, tubular damage, inflammatory infiltration) by Hematoxylin and eosin staining. In this study treatment group(C) with liraglutide appeared significant decreased (P< 0.05) in glomerulosclerosis, tubulointerstitial, and inflammatory infiltration after 28 day of treatment. In conclusion, liraglutide is effective in reducing inflammation and apoptosis which associate with chronic renal development as well as renoprotection by glycemic control which is indirectly effect.

Acute liver disease is characterized by loss of liver function within days or weeks however, in the patient who is not previously diagnosed, its less common compared with chronic liver failure, which developed slowly and irreversible process. It’s caused by   drug-induced liver damage (DILI) therefore identifying liver injury is challenging for clinical treatment and diagnosis. The major causes of liver failure involve toxic metabolites of some medications that consumed Adenosine Tri Phosphate (ATP) compared with normal conditions and increased oxidative stress due to overexpression of MicroRNAs, it is necessary to do complete diagnosis of patients. Biomarker parameters can be utilized to validate liver damage like microRNAs (miRNAs) analysis, it is a more receptive marker because increased earlier than the transaminases enzymes allowing for a more accurate diagnosis.  we summarized recent signs of progress disease concerning the role of miRNA as a novel DILI biomarker, the miRNA levels can be measured in plasma, saliva, urine, fetal fluid (amniotic), as well as other materials either in human or animals like mice, rats which significantly elevate during illness, therefore, provide e specific biomarker of hepatoinjury.