Naringin attenuates oxaliplatin-induced nephrotoxicity and hepatotoxicity: A molecular, biochemical, and histopathological approach in a rat model.

Oxaliplatin (OXL) is a significant therapy agent for the worldwide increase in cancer cases. Naringin (4',5,7-trihydroxy flavonon 7-rhamnoglucoside, NRG) has a wide range of biological and pharmacological activities, including antioxidant and anti-inflammatory potentials. This research aimed to investigate NRG activity in OXL-induced hepatorenal toxicity. Accordingly, OXL (4 mg/kg b.w.) in 5% glucose was injected intraperitoneally on the first, second, fifth, and sixth days, and NRG (50 and 100 mg/kg b.w.) was given orally 30 min before to treatment. Biochemical, genetic, and histological methods were utilized to investigate the function tests, oxidant/antioxidant status, inflammation, apoptosis, and endoplasmic reticulum (ER) stress pathways in kidney and liver tissues. Administration of NRG demonstrated an antioxidant effect by increasing the activities of OXL-induced reduced antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and decreasing the elevated lipid peroxidation parameter malondialdehyde levels. Nuclear factor-κB, tumor necrosis factor-α, interleukin-1ß, and inducible nitric oxide synthase levels increased in OXL administered groups but reduced in NRG-treated groups. In the OXL-administered groups, NRG reduced the apoptosis-inducing factors Caspase-3 and B-cell lymphoma 2 (Bcl-2)-associated X protein levels, while elevating the antiapoptotic factor Bcl-2 levels. OXL triggered prolonged ER stress by increasing the levels of ER stress parameters activating transcription factor 6, protein kinase R-like ER kinase, inositol-requiring enzyme 1α, and glucose-regulated protein 78. Therefore, with the NRG administration, this activity was reduced and the ER stress level decreased. Taken together, it was found that OXL induced toxicity by increasing the levels of urea and creatinine, alanine transaminase, aspartate aminotransferase, and alkaline phosphatase activities, inflammation, apoptosis, ER stress, and oxidants in the liver and kidney tissue, and NRG had a protective effect by reversing the deterioration in these pathways.

The ameliorative effect of carvacrol on sodium arsenite-induced hepatotoxicity in rats: Possible role of Nrf2/HO-1, RAGE/NLRP3, Bax/Bcl-2/Caspase-3, and Beclin-1 pathways.

Arsenic is a toxic environmental pollutant heavy metal, and one of its critical target tissues in the body is the liver. Carvacrol is a natural phytocompound that stands out with its antioxidant, anti-inflammatory, and antiapoptotic properties. The current study aims to investigate the protective feature of carvacrol against sodium arsenite-induced liver toxicity. Thirty-five Sprague-Dawley male rats were divided into five groups: Control, Sodium arsenite (SA), CRV, SA + CRV25, and SA + CRV50. Sodium arsenite was administered via oral gavage at a dose of 10 mg/kg for 14 days, and 30 min later, CRV 25 or 50 mg/kg was administered via oral gavage. Oxidative stress, inflammation, apoptosis, autophagy damage pathways parameters, and liver tissue integrity were analyzed using biochemical, molecular, western blot, histological, and immunohistological methods. Carvacrol decreased sodium arsenite-induced oxidative stress by suppressing malondialdehyde levels and increasing superoxide dismutase, catalase, glutathione peroxidase activities, and glutathione levels. Carvacrol reduced inflammation damage by reducing sodium arsenite-induced increased levels of NF-κB and the cytokines (TNF-α, IL-1ß, IL-6, RAGE, and NLRP3) it stimulates. Carvacrol also reduced sodium arsenite-induced autophagic (Beclin-1, LC3A, and LC3B) and apoptotic (P53, Apaf-1, Casp-3, Casp-6, Casp-9, and Bax) parameters. Carvacrol preserved sodium arsenite-induced impaired liver tissue structure. Carvacrol alleviated toxic damage by reducing sodium arsenite-induced increases in oxidative stress, inflammation, apoptosis, and autophagic damage parameters in rat liver tissues. Carvacrol was also beneficial in preserving liver tissue integrity.

Protective effects of naringin on colistin-induced damage in rat testicular tissue: Modulating the levels of Nrf-2/HO-1, AKT-2/FOXO1A, Bax/Bcl2/Caspase-3, and Beclin-1/LC3A/LC3B signaling pathways.

Antimicrobial agent resistance has become a growing health issue across the world. Colistin (COL) is one of the drugs used in the treatment of multidrug-resistant bacteria resulting in toxic effects. Naringin (NRG), a natural flavonoid, has come to the fore as its antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of the present study was to determine whether NRG has protective effects on COL-induced toxicity in testicular tissue. Thirty-five male Spraque rats were randomly divided into five groups (n = 7 per group): Control, COL, NRG, COL + NRG 50, COL + NRG 100. COL (15 mg/kg b.w., i.p., once per/day), and NRG (50 or 100 mg/kg, oral, b.w./once per/day) were administered for 7 days. The parameters of oxidative stress, inflammation, apoptosis, and autophagic damage were evaluated by using biochemical, molecular, western blot, and histological methods in testicular issues. NRG treatment reversed the increased malondialdehyde level and reduced antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione) levels due to COL administration (p < 0.001), and oxidative stress damage was mitigated. Nuclear factor erythroid 2-related factor-2 pathway, one of the antioxidant defence systems, was stimulated by NRG (p < 0.001). NRG treatment reduced the levels of markers for the pathways of apoptotic (p < 0.001) and autophagic (p < 0.001) damages induced by COL. Sperm viability and the live/dead ratio were reduced by COL but enhanced by NRG treatment. Testicular tissue integrity was damaged by COL but showed a tendency to improve by NRG. In conclusion, COL exhibited toxic effect on testicular tissue by elevating the levels of oxidative stress, apoptosis, autophagy, inflammation, and tissue damage. NRG demonstrated a protective effect by alleviating toxic damage.

Beneficial effects of quercetin on vincristine-induced liver injury in rats: Modulating the levels of Nrf2/HO-1, NF-kB/STAT3, and SIRT1/PGC-1α.

Our experimental objective was to investigate the hepatotoxic effect of vincristine (VCR) administration in rats and determined whether combined therapy with Quercetin (Quer) ensured protection. Five groups with seven rats each were used for this purpose, and experimental groups were formulated as follows: Control group; Quer group; VCR group; VCR plus Quer 25 group; VCR plus Quer 50 group. The results showed that VCR significantly increased the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes. Besides, VCR caused considerable increases in the malondialdehyde (MDA) contents, along with significant decreases in reduced glutathione levels, superoxide dismutase, catalase, and glutathione peroxidase enzyme activities in the rat livers. Quer treatment in VCR toxicity markedly decreased the activity of ALT, AST, ALP enzymes, and MDA contents and enhanced the activities of antioxidant enzymes. The results also showed that VCR significantly increased the levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3 and decreased the expression of Bcl2 and levels of Nrf2, HO-1, SIRT1, and PGC-1α. Compared to the VCR group, Quer treatment exhibited significantly lower levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3, and higher levels of Nrf2, HO-1, SIRT1, and PGC-1α. In conclusion, our study demonstrated that Quer could alleviate the harmful effects of VCR via activation of NRf2/HO-1 and SIRT1/PGC-1α pathways, and via attenuation of oxidative stress, apoptosis, autophagy, and NF-kB/STAT3 pathways.

Protective effect of naringin against oxaliplatin-induced peripheral neuropathy in rats: A behavioral and molecular study.

Oxaliplatin (OXL) is a chemotherapeutic drug used for metastatic and other types of cancer, but it causes peripheral neuropathy as a dose-limiting side effect. Herein, we used the rat model of OXL-induced peripheral neuropathy to demonstrate the protective effects of naringin (NRG) in this neuropathy. In this study, rats were injected with OXL (4 mg/kg, body weight, i.p.) in 5% glucose solution 30 min after oral administration of NRG (50 and 100 mg/kg, body weight) on the 1st, 2nd, 5th, and 6th days. OXL caused sensory and motor neuropathy (as revealed by the hot plate, tail flick, rota-rod, and cold hyperalgesia tests) in the sciatic nerve of rats. Coadministration of oral NRG alleviated OXL-induced sensory and motor neuropathy. Levels of superoxide dismutase, catalase, glutathione peroxidase, nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, nuclear factor-κ B, tumor necrosis factor-α, interleukin-1ß, Bax, Bcl-2, caspase-3, paraoxonase, mitogen-activated protein kinase 14, neuronal nitric oxide synthase (nNOS), acetylcholinesterase, and arginase 2 in the sciatic nerve tissues were assessed by real-time polymerase chain reaction. Moreover, the protein levels of caspase-3, Bax, Bcl-2, intercellular adhesion molecules-1, glial fibrillary acidic protein, and nNOS were examined by Western blot analysis. NRG treatment significantly improved all the above-mentioned parameters and reduced OXL-induced oxidative stress, inflammation, and apoptosis in the sciatic nerve tissue. In conclusion, this study demonstrated that NRG significantly attenuated OXL-induced peripheral neuropathy and might be considered as a new protective agent to prevent the OXL-induced peripheral neuropathy.

The antiapoptotic and antioxidant effects of eugenol against cisplatin-induced testicular damage in the experimental model.

Testicular dysfunction or damage is among the critical side effects of chemotherapeutic drugs like cisplatin. This study was mapped out to assess the possible therapeutic effect of eugenol on cisplatin-induced testicular damage. In this experimental study, a single dose of cisplatin (15 mg/kg) was given intraperitoneally. After 72 hr of cisplatin injection, rats were sacrificed and testis tissues were removed. Tissues were examined by biochemical, histopathological and immunohistochemical methods. While tissue lipid peroxidation product and apoptotic marker levels increased, antioxidant enzyme activities of testis tissue were decreased in the cisplatin group. Additionally, histopathological damage was also determined in testis tissue. Contrary to all these results, the severity of damage in the tissue was reduced histopathologically owing to eugenol treatment. The lipid peroxidation decreased and antioxidant enzyme activities increased in the eugenol treatment group. It has been determined that eugenol has a therapeutic effect on oxidative stress and apoptosis against cisplatin-induced testicular damage.