Protective effects of valproic acid on 6‐hydroxydopamine‐induced neuroinjury

Purpose: To investigation the protective effects of hesperetin against 6-hydroxydopamine (6-OHDA)- induced neurotoxicity. Methods: SH-SY5Y cells were incubated with 6-OHDA to create an in vitro model of neurotoxicity. This model was used to test the neuroprotective effects of hesperetin. Cell viability was assessed by MTT and lactate dehydrogenase (LDH) release assays. Flow cytometry and western blot were used to quantify apoptosis. Oxidative stress was evaluated by determining intracellular glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS). Results: In SH-SY5Y cells, treatment with 6-OHDA decreased cell viability and promoted LDH release. However, exogenous hesperetin protected against 6-OHDA-mediated toxicity. Similarly, although incubation with 6-OHDA induced apoptosis and increased cleaved caspase-3 and -9 levels, treatment with hesperetin protected against these effects. Treatment with 6-OHDA also led to significant oxidative stress, as indicated by reduced GSH and SOD levels and increased MDA and ROS levels in SH-SY5Y cells. However, these changes were reversed by pre-treatment with hesperetin. Of interest, hesperetin led to changes in 6-OHDA-induced expression of NRF2, heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCL) catalytic subunit (GCLC), and GCL modulatory (GCLM). Conclusion: Hesperetin protects against cell toxicity, apoptosis, and oxidative stress via activation of NRF2 pathway in a 6-OHDA-induced model of neurotoxicity. Future studies should investigate the use of hesperetin as a potential therapeutic approach for prevention or management of Parkinson’s disease. Keywords: Hesperetin, 6-OHDA, Neurotoxicity, NRF2, Parkinson’s disease

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Rhanterium suaveolens, Vitamin E and C Pretreatment Prevents Valproic Acid Induced Renal Oxidant Damage

The Natural Products Journal ◽

10.2174/2210315510999200629205136 ◽

2020 ◽

Vol 10 ◽

Author(s):

Amel Amrani ◽

Ouahiba Benaissa ◽

Nassima Boubekri ◽

Fadila Benayache ◽

Samir Benayache ◽

...

Keyword(s):

Oxidative Stress ◽

Valproic Acid ◽

Vitamin E ◽

Serum Creatinine ◽

Natural Antioxidants ◽

Control Group ◽

Protective Effects ◽

Butanol Extract ◽

Renal Tubular ◽

Vit C

Background: Long-term administration of valproic acid (VPA) is known to promote renal tubular injury mediated by increase in renal oxidative stress. Recent evidence indicates that natural antioxidants are alternative to attenuate oxidative stress and kidney damage. Objective: This study was performed to investigate the protective effects of n-butanol extract of Rhanterium suaveolens, vitamin E (Vit E) and vitamin C (Vit C) against VPA induced nephrotoxicity in mice. Methods: Mice were randomly divided into 6 groups (n: 8) and treated daily for 12 days. They received VPA (300 mg/kg intraperitoneally (ip)), buthanolic extract (100 mg/kg), Vit E (100 mg/kg), and Vit C (16.66 mg/kg) 1h prior to administration of VPA. On day 13, blood and Kidneys samples were analyzed for biomarker levels and histopathological changes. Kidneys homogenates were used for determination of oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level and glutathione peroxidase (GPx) activity. Result: Treatment with VPA showed a significant increase in the levels of serum creatinine, urea and malondialdehyde (MDA) and decreasing the enzymatic activity (GPx) as well as GSH levels in kidney with marked necrotic epithelial cells and infiltration in kidney sections as compared to the control group. Pretreatment with the n-butanol extract of R. suaveolens, Vit C or Vit E 1 h prior to administration of VPA showed a significant decrease in the levels of serum creatinine, urea, and MDA, as well as an improvement in the antioxidant elements and histological changes compared to those previously seen in the group treated with VPA alone. Conclusion: It is concluded that n-butanol extract of R. suaveolens, Vit C and Vit E pretreatment effectively improved renal function and tissue oxidative damage caused by VPA.

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