Molecular Studies on the Nephroprotective Potential of Celastrus paniculatus against Lead-Acetate-Induced Nephrotoxicity in Experimental Rats: Role of the PI3K/AKT Signaling Pathway

Abstract

Chemicals can induce nephrotoxicity, with damage to different segments of the nephron and deterioration of renal function. Nephrotoxicity due to exposure to a toxin such as carbon tetrachloride, sodium oxalate, or heavy metals is the most common cause of kidney injury. The current study aimed to evaluate the protective effects of Celastrus paniculatus seed extract against lead-acetate-induced nephrotoxicity by evaluating the histopathology, immunohistochemistry, ultrastructure, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Twenty-four rats were divided into four groups (n = 6 per group): group 1 contained normal animals and served as the control; group 2 received lead acetate (30 mg/kg body weight (b.w.)/day, oral); group 3 received lead acetate and the standard drug N-acetylcysteine (NAC, 200 mg/kg b.w./day, oral); and group 4 received lead acetate and the ethanolic extract of C. paniculatus seed (EECP; 800 mg/kg b.w./day, oral). Treatment was given for 28 consecutive days. The data were analyzed using one-way analysis of variance with SIGMA PLOT 13 using SYSTAT software followed by Newman–Keul’s test for comparison between the groups. EECP ameliorated the adverse changes caused by lead acetate. PI3K and AKT messenger RNA (mRNA) levels were diminished in lead-acetate-treated rats. Treatment with EECP inhibited the occurrence of shrunken cells, the atrophy of glomeruli, and degenerative changes in renal tubules caused by lead acetate. Interestingly, the PI3K and AKT mRNA levels were significantly increased in EECP-treated animals. Our results clearly evidence for the first time that C. paniculatus seed extract inhibits lead-acetate-induced detrimental changes in kidneys by regulating PI3K/AKT signaling pathways.

Celastrus paniculatus seed extract exhibits neuroprotective effects against MPP+‑induced apoptotic cell death via GSK‑3β in a Parkinson's disease model

“…In the present study, MPP + treatment reduced the expression levels of p-GSK-3β (Ser9). Moreover, this result was consistent with previous evidence that CPSE treatment inhibits the occurrence of lead acetate-induced degenerative changes in the renal tubules with significantly increased PI3K and AKT mRNA expression levels in CP-treated rats (19) This previous finding indicated that CPSE may inhibit lead acetate-induced detrimental changes in the kidneys by regulating the PI3K/AKT signaling pathway (19). Since the phosphorylation status of GSK-3β is primarily regulated by AKT, and various stimulating factors activate the PI3K/AKT pathway (5), the present study suggested that CPSE inhibited the MPP + -induced model of PD in SH-SY5Y cells by regulating PI3K/AKT/GSK-3β signaling.…”

The Possible Ameliorative Role of Chrysin and Zinc on Lead Acetate Induced Nephrotoxicity in Adult Albino Rats (Biochemical, Histological and Immunohistochemical study)

“…This work revealed marked increase in the amount of collagen fibers distribution in the renal sections stained by Masson Trichome in group (II). Similarly, Balaji et al (29) documented that the kidneys' entire collagen content significantly increased in lead acetatetreated rats compared with control rats. But conversely, the renal sections from chrysin treated group and zinc treated group showed moderate increase in the density and distribution of collagen fibers.…”

The Anti-Rheumatic Drug, Leflunomide, Induces Nephrotoxicity in Mice via Upregulation of TGFβ-Mediated p53/Smad2/3 Signaling

“…The kidney is a vulnerable vital organ in drug elimination; therefore, chemical exposure to drugs and their metabolites will jeopardize the urinary tract system [ 18 , 19 ]. Toxic damage (either acute or chronic) to the kidney is attributed to various substances, such as hydrocarbons, heavy metals, and proven nephrotoxic drugs, as well as aflatoxins that might result in renal cancer or failure [ 20 , 21 , 22 , 23 ].…”