Role of some natural anti-oxidants in the down regulation of Kim, VCAM1, Cystatin C protein expression in lead acetate-induced acute kidney injury.

BACKGROUND: Lead is a dangerous systemic toxicant and can provoke life-threatening renal injury. The plan of this study was to evaluate the potential impact of curcumin (CRMN) and L-ascorbic acid (L-ascb) alone or together to counteract lead acetate (Pb-acetate)-induced renal damage in rats and to find out the underlying mechanisms of action of these nutraceuticals. METHODS: Pb-acetate (100 mg/kg/day, i.p.) was injected in male rats along with L-ascb (250 mg/kg/day) and/or CRMN (200 mg/kg/day) orally for 7 days. RESULTS: Pb-acetate administration increased serum urea, creatinine and uric acid. Renal tissue showed a marked depletion in reduced glutathione level and superoxide dismutase activity and elevation in nitric oxide and malondialdehyde levels. Serum C-reactive protein and IL-1ß levels were elevated. Up-regulation of the expression of kidney injury molecule, vascular adhesion molecule-1 and Cystatin C were noticed after Pb-acetate administration. DNA fragmentation was also increased in renal tissues. Histopathological examination revealed a destructed partial layer of Bowman's capsule, proximal and distal convoluted tubules. Treatment with the aforementioned antioxidants ameliorated most of the altered measured biomarker levels. CONCLUSION: Interestingly, the combination of L-ascb and CRMN showed the superlative protective effect against Pb-acetate-induced nephrotoxicity.

Arctium lappa Root Extract Prevents Lead-Induced Liver Injury by Attenuating Oxidative Stress and Inflammation, and Activating Akt/GSK-3ß Signaling.

Arctium lappa L (A. lappa) is a popular medicinal plant with promising hepatoprotective activity. This study investigated the protective effect of A. lappa root extract (ALRE) on lead (Pb) hepatotoxicity, pointing to its ability to modulate oxidative stress, inflammation, and protein kinase B/Akt/glycogen synthase kinase (GSK)-3ß signaling. Rats received 50 mg/kg lead acetate (Pb(Ac)2) and 200 mg/kg ALRE or vitamin C (Vit. C) for 7 days, and blood and liver samples were collected. Pb(Ac)2 provoked hepatotoxicity manifested by elevated serum transaminases and lactate dehydrogenase, and decreased total protein. Histopathological alterations, including distorted lobular hepatic architecture, microsteatotic changes, congestion, and massive necrosis were observed in Pb(II)-induced rats. ALRE ameliorated liver function and prevented all histological alterations. Pb(II) increased hepatic lipid peroxidation (LPO), nitric oxide (NO), caspase-3, and DNA fragmentation, and serum C-reactive protein, tumor necrosis factor-α, and interleukin-1ß. Cellular antioxidants, and Akt and GSK-3ß phosphorylation levels were decreased in the liver of Pb(II)-induced rats. ALRE ameliorated LPO, NO, caspase-3, DNA fragmentation and inflammatory mediators, and boosted antioxidant defenses in Pb(II)-induced rats. In addition, ALRE activated Akt and inhibited GSK-3ß in the liver of Pb(II)-induced rats. In conclusion, ALRE inhibits liver injury in Pb(II)-intoxicated rats by attenuating oxidative injury and inflammation, and activation of Akt/GSK-3ß signaling pathway.

Cross Talk Between TGF-ß and JAK Expressions and Nepherotoxicity Induced by Tetrachloromethane: Role of Phytotherapy.

The aim of the current study is to assess the effectiveness of milk thistle seeds (Mth) in combination with Taraxacum officinale (Tof) and/or Camellia sinensis (Csin) against tetrachloromethane (Tcm) renotoxicity in rats. Tetrachloromethane was injected in a single dose, followed by 1-month treatments with Mth, Tof, and Csin alone or in combination. Serum urea, uric acid, and creatinine levels were significantly increased matched with the control group. Masson trichrome stain revealed increase in the deposition of fibrous tissue in the interstitium between the tubules and the renal corpuscles. Immunohistochemical analysis of kidney tissues revealed that Tcm induced an increase in the immune response of tumor growth factor ß (TGF-ß) and Janus kinase (JAK) protein expressions and cysteine-aspartic acid protease 3 (caspase 3), while B-cell lymphoma 2 (Bcl2) was downregulated. Treatment with the antioxidants in question either alone or in combination ameliorated all kidney function parameters and showed mild immune reactivity toward TGF-ß and JAK protein expressions in blood vessels and glomeruli in the kidney tissues and downregulated caspase 3 and activated Bcl2 protein expression. The combination regimen of the 3 antioxidants showed the most significant renoprotective effect. This was also confirmed histopathologically. It was concluded that the antioxidant mixture is considered as a promising candidate toward renal dysfunction and immune reactivity induced by Tcm and other toxicants.

Evaluation of the renoprotective effect of nano turmeric against toxic dose of copper sulfate: Role of vascular cell adhesion molecule-1, kidney injury molecule-1, and signal transducer and activator of transcription 3 protein expressions.

The aim of this study was to compare the potential renoprotective effects of turmeric (TM) and nano turmeric (NTM) with those of desferrioxamine (DSM) against copper sulfate (CS)-induced toxicity. Rats were administered a toxic dose of CS with TM, NTM, and DSM for 1 week. Next, serum-urea creatinine, uric acid, interleukin (IL)-10, c-reactive protein (CRP), and caspase-3 levels; renal nitric oxide (NO), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), vascular cell adhesion molecule-1 (VCAM-1), kidney injury molecule (KIM)-1, signal transducer and activator of transcription 3 (STAT-3) protein expression; and nuclear factor (NF)-κB and B-cell lymphoma -2 (Bcl-2) messenger RNA expression levels were estimated. Administration of the investigated antioxidants downregulated the marked increase in urea, creatinine, uric acid, CRP, caspase-3, NO, MDA, VCAM-1, kidney injury molecule (KIM-1), STAT-3, NF-κB, and DNA fragmentation, and increased Bcl-2, IL-10, GSH, and SOD levels induced by CS. The histopathological examination confirmed the effects of the antioxidants on the investigated biochemical parameters. Interestingly, NTM exhibited a superior renoprotective effect, which was comparable with that of DSM. In conclusion, NTM was shown to be a promising candidate against CS-induced toxicity, and several molecular mechanisms were implicated in the CS-induced renotoxicity as well as the treatment effects of NTM.

Amelioration of panadol-induced nephrotoxicity via down-regulation of Bax/Bcl2 ratio with some antioxidants.

BACKGROUND: Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, Thymoquinone (THQ), Curcumin (CUR) and α-Lipoic acid (LA) either alone or in combination against APAP nephrotoxicity, focused on modulation of Bax/Bcl2 pathway. METHODS: APAP was administrated at a single dose then treated with the fore mentioned antioxidants. RESULTS: APAP administration increased serum creatinine, urea, uric acid, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels compared to control group. There is a marked depletion of reduced glutathione (GSH) levels and superoxide dismutase activity (SOD), Bax level was overexpressed, whereas Bcl2 was downregulated in renal tissue. Histopathological examination of the kidney tissue supported these biochemical findings. Treatment with the fore mentioned anti-oxidants ameliorated most of the previous evaluated parameters and returned the kidney nearly to its normal architecture. CONCLUSION: The expression of Bax and Bcl2 is considered one of the mechanisms underlying APAP-induced nephrotoxicity. The administration of THQ along with CUR could be a promising antidote for APAP renal damage through their antioxidant potential.