Recombinant human erythropoietin and interferon-β-1b protect against 3-nitropropionic acid-induced neurotoxicity in rats: possible role of JAK/STAT signaling pathway

Abstract

Abstract3-Nitropropionic acid (3-NP) model serves as a beneficial tool to evaluate the effect of novel treatments for Huntington’s disease (HD). The aim of the present study was to demonstrate the neuroprotective effect of recombinant human erythropoietin (rhEPO) and interferon-beta-1b (IFN-β-1b) in 3-NP-induced neurotoxicity in rats. Rats were injected with 3-NP (10 mg/kg/day, i.p) for 2 weeks and were divided into five subgroups; the first served as the HD group, the second received rhEPO (5000 IU/kg/every other day, i.p.) for 2 weeks, the third received rhEPO starting from the 5th day of 3-NP injection, the fourth received IFN-β-1b (300,000 units, every day other day, s.c) for 2 weeks, and the last received IFN-β-1b starting from the 5th day of 3-NP injection. All treatments significantly improved motor and behavior performance of rats. Moreover, all treatments markedly restored mitochondrial function as well as brain-derived neurotrophic factor level, and reduced oxidative stress biomarkers, pro-inflammatory mediators, nuclear factor kappa B expression, caspase-3, and Bax/Bcl2 ratio in the striatum. In conclusion, the present study demonstrates the neuroprotective potential of rhEPO or IFN-β-1b on 3-NP-induced neurotoxicity in rats. Furthermore, our study suggests that activation of JAK2/STAT3 or JAK1/STAT3 may contribute to the neuroprotective activity of rhEPO or IFN-β-1b, respectively. We also found that early treatment with rhEPO did not confer any benefits compared with late rhEPO treatment, while early IFN-β-1b showed a marked significant benefit compared with late IFN-β-1b.

Azilsartan Attenuates 3-Nitropropinoic Acid-Induced Neurotoxicity in Rats: The Role of IĸB/NF-ĸB and KEAP1/Nrf2 Signaling Pathways

“…3-NP-treated rats showed elevated expression of AT1R and NF-ĸB p65 along with diminished IκB expression in the striatum with the consequent elevation of downstream pro-inflammatory cytokines including TNF-α and IL-1β. These results are in line with previous ones demonstrating significant elevation of NF-ĸB and pro-inflammatory mediators in 3-NP-treated rats [ 66 , 67 ]. However, Azil showed an anti-inflammatory activity via reducing the AT1R and NF-ĸB p65 expression and the TNF-α and IL-1β levels along with increasing the expression of IκB.…”

“…Since striatal neurons are extremely sensitive to derangement in energy metabolism, such mitochondrial dysfunction increase the susceptibility of striatum to acute intoxication with mitochondrial toxins such as 3-NP in both experimental and clinical studies [ 80 ]. Herein, 3-NP administration was associated with inhibition of striatal SDH activity in rats which go in line with previous studies [ 49 , 67 , 80 ], an effect that was reversed by Azil restoring mitochondrial activity. These findings comply with previous ones demonstrating that treatment with Azil significantly decreased the activity of SDH in high-fat diet (HFD)-induced sarcopenic obesity in rats [ 81 ].…”

Europinidin Mitigates 3-NPA-Induced Huntington’s Disease Symptoms in Rats: A Comprehensive Analysis of Oxidative Stress, Mitochondrial Enzyme Complex Activity, Pro-Inflammatory Markers and Neurotransmitter Alterations

“…Europinidin might influence neurotransmitter levels by inhibiting AChE activity, increasing GABA levels, and promoting DA synthesis or release. These actions could help restore neurotransmitter balance, which is often disrupted in HD [ 45 , 46 , 47 , 48 , 49 , 50 ].…”

The Potential Neuroprotective Effect of Cyperus esculentus L. Extract in Scopolamine-Induced Cognitive Impairment in Rats: Extensive Biological and Metabolomics Approaches

“…The MWM test is used to evaluate spatial learning and memory in animal models [ 99 , 100 ]. The maze consisted of a stainless-steel circular pool (210 cm in diameter, 51 cm high) divided into four equal quadrants and filled with water (26 ± 2 °C) to a depth of 35 cm.…”