N-acetylcysteineamide protects against manganese-induced toxicity in SHSY5Y cell line

Maddirala, Yasaswi; Tobwala, Shakila; Erçal, Nuran

doi:10.1016/j.brainres.2015.02.006

Cited by 35 publications

(25 citation statements)

References 65 publications

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“…Mel pre-treatment was found to significantly inhibit the mitochondrial to cytosol transfer when compared to Oxa-treatment alone. This observation is similar to previous studies that have also found Mel to downregulate Cyt c in SH-SY5Y cells challenged with neurotoxicants [45, 46]. …”

Section: Discussionsupporting

confidence: 92%

“…Evidence of this property has been shown by the ability of Mel to directly quench a variety of ROS species, including singlet oxygen, hydroxyl radical, peroxyl radicals and superoxide anion and H2O2 in SH-SY5Y cells [45, 46]. A possible event in early apoptosis stages is the appearance of phosphatidyl serine on the outer surface of the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

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Melatonin pre-treatment mitigates SHSY-5Y cells against oxaliplatin induced mitochondrial stress and apoptotic cell death

et al. 2017

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Oxaliplatin (Oxa) treatment to SH-SY5Y human neuroblastoma cells has been shown by previous studies to induce oxidative stress, which in turn modulates intracellular signaling cascades resulting in cell death. While this phenomenon of Oxa-induced neurotoxicity is known, the underlying mechanisms involved in this cell death cascade must be clarified. Moreover, there is still little known regarding the roles of neuronal mitochondria and cytosolic compartments in mediating Oxa-induced neurotoxicity. With a better grasp of the mechanisms driving neurotoxicity in Oxa-treated SH-SY5Y cells, we can then identify certain pathways to target in protecting against neurotoxic cell damage. Therefore, the purpose of this study was to determine whether one such agent, melatonin (Mel), could confer protection against Oxa-induced neurotoxicity in SH-SY5Y cells. Results from the present study found Oxa to significantly reduce SH-SY5Y cell viability in a dose-dependent manner. Alternatively, we found Mel pre-treatment to SH-SY5Y cells to attenuate Oxa-induced toxicity, resulting in a markedly increased cell viability. Mel exerted its protective effects by regulating reactive oxygen species (ROS) production and reducing superoxide radicals inside Oxa-exposed. In addition, we observed pre-treatment with Mel to rescue Oxa-treated cells by protecting mitochondria. As Oxa-treatment alone decreases mitochondrial membrane potential (Δψm), resulting in an altered Bcl-2/Bax ratio and release of sequestered cytochrome c, so Mel was shown to inhibit these pathways. Mel was also found to inhibit proteolytic activation of caspase 3, inactivation of Poly (ADP Ribose) polymerase, and DNA damage, thereby allowing SH-SY5Y cells to resist apoptotic cell death. Collectively, our results suggest a role for melatonin in reducing Oxa induced neurotoxicity. Further studies exploring melatonin’s protective effects may prove successful in eliciting pathways to further alter the neurotoxic pathways of platinum compounds in cancer treatment.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Melatonin pre-treatment mitigates SHSY-5Y cells against oxaliplatin induced mitochondrial stress and apoptotic cell death

et al. 2017

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“…In contrast, N-acetylcysteine amide (NACA), an analog of NAC, has been shown to be more effective than NAC, owing to its neutral amide group, which increases its lipophilicity and, consequently, its penetration into cell membranes. This has been verified in previous studies, as well as its ability to chelate Cu 2+ , scavenge free-radicals, and protect against oxidative stress [29–36]. Our lab has demonstrated NACA’s improved antioxidant ability compared to that of NAC [33, 37].…”

Section: Introductionsupporting

confidence: 79%

Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide in Wistar rats

Maddirala¹,

Tobwala²,

Karacal³

et al. 2017

BMC Ophthalmol

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BackgroundThe present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups.MethodsForty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups opened their eyes. N-acetylcysteine amide eye drops were administered beginning on week 3 until the end of week 4 (postpartum days 15 to 30), and the rats were sacrificed at the end of week 4. Lenses were isolated and examined for oxidative stress parameters such as glutathione, lipid peroxidation, and calcium levels along with the glutathione reductase and thioltransferase enzyme activities. Casein zymography and Western blot of m-calpain were performed using the water soluble fraction of lens proteins.ResultsMorphological examination of the lenses in the NACA-treated group indicated that NACA was able to reverse the cataract grade. In addition, glutathione level, thioltransferase activity, m-calpain activity, and m-calpain level (as assessed by Western blot) were all significantly higher in the NACA-treated group than in the sodium selenite-induced cataract group. Furthermore, sodium selenite- injected rat pups had significantly higher levels of malondialdehyde, glutathione reductase enzyme activity, and calcium levels, which were reduced to control levels upon treatment with NACA.ConclusionsThe data suggest that NACA has the potential to significantly improve vision and decrease the burden of cataract-related loss of function. Prevention and reversal of cataract formation could have a global impact. Development of pharmacological agents like NACA may eventually prevent cataract formation in high-risk populations and may prevent progression of early-stage cataracts. This brings a paradigm shift from expensive surgical treatment of cataracts to relatively inexpensive prevention of vision loss.

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“…In contrast, N-acetylcysteine amide (NACA), an analog of NAC, has been shown to be more effective than NAC, owing to its neutral amide group, which increases its lipophilicity and, consequently, its penetration into cell membranes. This has been verified in previous studies, as well as its ability to chelate Cu 2+ , scavenge free-radicals, and protect against oxidative stress [29][30][31][32][33][34][35][36]. Our lab has demonstrated NACA's improved antioxidant ability compared to that of NAC [33,37].…”

supporting

confidence: 80%

Prevention and reversal of selenite‐induced cataracts by N‐acetylcysteine amide in Wistar rats

Maddirala

Tobwala

Karacal

et al. 2016

Acta Ophthalmologica

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Background: The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups. Methods: Forty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups opened their eyes. N-acetylcysteine amide eye drops were administered beginning on week 3 until the end of week 4 (postpartum days 15 to 30), and the rats were sacrificed at the end of week 4. Lenses were isolated and examined for oxidative stress parameters such as glutathione, lipid peroxidation, and calcium levels along with the glutathione reductase and thioltransferase enzyme activities. Casein zymography and Western blot of m-calpain were performed using the water soluble fraction of lens proteins. Results: Morphological examination of the lenses in the NACA-treated group indicated that NACA was able to reverse the cataract grade. In addition, glutathione level, thioltransferase activity, m-calpain activity, and m-calpain level (as assessed by Western blot) were all significantly higher in the NACA-treated group than in the sodium selenite-induced cataract group. Furthermore, sodium selenite-injected rat pups had significantly higher levels of malondialdehyde, glutathione reductase enzyme activity, and calcium levels, which were reduced to control levels upon treatment with NACA.

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N-acetylcysteineamide protects against manganese-induced toxicity in SHSY5Y cell line

Cited by 35 publications

References 65 publications

Melatonin pre-treatment mitigates SHSY-5Y cells against oxaliplatin induced mitochondrial stress and apoptotic cell death

Melatonin pre-treatment mitigates SHSY-5Y cells against oxaliplatin induced mitochondrial stress and apoptotic cell death

Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide in Wistar rats

Prevention and reversal of selenite‐induced cataracts by N‐acetylcysteine amide in Wistar rats

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