Research Article
Exploring the neuroprotective effects of black garlic ethanol extract on acrylamide-induced brain damage through apoptotic and neurodegenerative pathways
Abstract
This research focused on exploring the therapeutic impact of black garlic ethanol extract (BGE) on the brain tissue of rats exposed to acrylamide (ACR). Twenty-four female rats were divided into four groups. Rats in the control group were given 1 ml of saline by oral gavage for 14 days. The BG group received 5 mg/200 g of BGE extract on a daily basis. The ACR group was administered 40 mg/kg of ACR daily. Rats in the BGE+ACR group received both 5 mg/200 g of BG extract and 40 mg/kg of ACR daily. Brain tissue samples were collected at the study's conclusion for histopathological, immunohistochemical, and biochemical analyses. Hematoxylin-eosin staining was performed to examine the general structure of the brain tissue. Erk1/2, p-ERK1/2, and c-fos were analyzed immunohistochemically; Bcl-2, Caspase-3, ATF6, CREB, and NfkB-p65 protein levels were analyzed by Western blotting; and MDA, SOD, CAT, GSH, TNF-α, IL-1β, and IL-6 activities and levels were analyzed using ELISA kits. It was determined that ACR application raised the levels of Erk1/2, p-ERK1/2, c-Fos, NfkB-p65, caspase-3, MDA, IL-6, IL-1-β, and TNF-α, and BGE supplementation decreased this increase. ACR exposure caused a decrease in Bcl-2, ATF6, CREB, CAT, GSH, and SOD expressions, and BGE supplementation prevented or increased this decrease. Based on the findings obtained, it can be said that the ethanol extract of black garlic has antioxidative and anti-inflammatory effects, prevents cell damage, and has positive effects on apoptosis in rat brain tissue.
Ethical Statement
The approval was obtained by the Animal Experiments Local Ethics Committee of Kafkas University, Faculty of Veterinary Medicine, on the date of 03.10.2023 with the ethics committee number 2023/11 and decision no 108 for this study.
References
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- Ahmed RA (2018): Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide. JOBAZ, 79, 1-8.
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- Al-Shehri SA (2021): Efficacy of black garlic extract on anti-tumor and anti-oxidant activity enhancement in rats. Clin Nutr Open Sci, 36, 126-139.
- Alturki HA, Elsawy HA, Famurewa AC (2022): Silymarin abrogates acrylamide‐induced oxidative stress‐mediated testicular toxicity via modulation of antioxidant mechanism, DNA damage, endocrine deficit and sperm quality in rats. Andrologia, 54, e14491.
- Aminuddin M, Partadiredja G, Sari D (2015): The effects of black garlic (Allium sativum L.) ethanol extract on the estimated total number of Purkinje cells and motor coordination of male adolescent Wistar rats treated with monosodium glutamate. Anat Sci Int, 90, 75-81.
- Aoudeh E, Oz E, Oz F (2023): Effect of beef patties fortification with black garlic on the polycyclic aromatic hydrocarbons (PAHs) content and toxic potency. Food Chem, 428, 136763.
- Begum SFM, Hemalatha S (2022): Gelidiella acerosa compounds target NFκB cascade in lung adenocarcinoma. Appl Biochem Biotechnol, 1-14.
- Chen Y, Zhang W, Guo X, et al (2019): The crosstalk between autophagy and apoptosis was mediated by phosphorylation of Bcl-2 and beclin1 in benzene-induced hematotoxicity. Cell Death Dis, 10, 772.
- Conti P, Ronconi G, Caraffa A, et al (2020): Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents, 34, 327-331.
- Edres HA, Taha NM, Lebda MA, et al (2021): The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats. Environ Sci Pollut Res, 28, 58768-58780.
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- Farag OM, Abd-Elsalam RM, El Badawy SA, et al (2021): Portulaca oleracea seeds’ extract alleviates acrylamide-induced testicular dysfunction by promoting oxidative status and steroidogenic pathway in rats. BMC Complement Altern Med, 21, 1-15.
- für Gesundheit HKBL (2023): Lebensmittel: Acrylamid.
- Gao J-G, Jiang Y, Zheng J-T, et al (2022): Pubertal exposure to acrylamide disrupts spermatogenesis by interfering with meiotic progression in male mice. Toxicol Lett, 358, 80-87.
- Gelen V, Özkanlar S, Kara A, et al (2023): Citrate-coated silver nanoparticles loaded with agomelatine provide neuronal therapy in acute cerebral ischemia/reperfusion of rats by inhibiting the oxidative stress, endoplasmic reticulum stress, and P2X7 receptor-mediated inflammasome. Environ Toxicol, 39, 1-13.
- Gelen V, Sengul E, Yildirim S, et al (2023): The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats. Iran J Basic Med Sci, 26, 1326-1333.
- Gelen V, Şengül E, Yıldırım S, et al (2021): The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice. Environ Sci Pollut Res, 28, 47046-47055.
- Gelen V, Yıldırım S, Şengül E, et al (2022): Naringin attenuates oxidative stress, inflammation, apoptosis, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats. Asian Pac J Trop Biomed, 12.
- Gezer A, Karadag-Sari E (2022): The role of amifostine in preventing radiotherapy-induced testicular tissue damage in rats. Biotech Histochem, 97, 215-221.
- Gezer A, Sari EK (2023): Investigation of apoptotic and autophagic effects of chronic roflumilast use on testicular tissue in rats by immunohistochemical and immunofluorescence methods. Iran J Basic Med Sci, 26, 276.
- Goudarzi M, Mombeini MA, Fatemi I, et al (2019): Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats. Neurol Res, 41, 419-428.
- Gu X, Nardone C, Kamitaki N, et al (2023): The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation. Science, 381, eadh5021.
- Gur C, Kandemir FM, Darendelioglu E, et al (2021): Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways. Environ Sci Pollut Res, 28, 49808-49819.
- Hermawati E, Sari DCR, Partadiredja G (2015): The effects of black garlic ethanol extract on the spatial memory and estimated total number of pyramidal cells of the hippocampus of monosodium glutamate-exposed adolescent male Wistar rats. Anat Sci Int, 90, 275-286.
- Hosseini E, Farid Habibi M, Babri S, et al (2022): Maternal stress induced anxiety-like behavior exacerbated by electromagnetic fields radiation in female rats offspring. PLoS One, 23, 17-18.
- Huang S-L, Chang T-C, Sun N-K (2023): Curcumin reduces paclitaxel resistance in ovarian carcinoma cells by upregulating SNIP1 and inhibiting NFκB activity. Biochem Pharmacol, 212, 115581.
- Kacar S, Sahinturk V (2021): The protective agents used against acrylamide toxicity: An in vitro cell culture study-based review. Cell Journal (Yakhteh), 23, 367.
- Kayacan S, Sener L, Melikoglu G, et al (2018): Induction of apoptosis by Centaurea nerimaniae extract in HeLa and MDA-MB-231 cells by a caspase-3 pathway. Biotech Histochem, 93, 311-319.
- Khakha N, Khan H, Kaur A, et al (2023): Therapeutic implications of phosphorylation-and dephosphorylation-dependent factors of cAMP-response element-binding protein (CREB) in neurodegeneration. Pharmacol Rep, 1-14.
- Kim J-J, Kang Y-J, Shin S-A, et al (2016): Phlorofucofuroeckol improves glutamate-induced neurotoxicity through modulation of oxidative stress-mediated mitochondrial dysfunction in PC12 cells. PLoS One, 11, e0163433.
- Kunle-Alabi OT, Akindele OO, Odoh MI, et al (2017): Comparative effects of coconut water and N-Acetyl cysteine on the hypothalamo-pituitary-gonadal axis of male rats. Songklanakarin J Sci Technol, 39, 759-764.
- Li F, Kim MR (2019): Effect of aged garlic ethyl acetate extract on oxidative stress and cholinergic function of scopolamine-Induced cognitive impairment in mice. Prev Nutr Food Sc, 24, 165.
- Lu K, Cho C-L, Liang C-L, et al (2007): Inhibition of the MEK/ERK pathway reduces microglial activation and interleukin-1-beta expression in spinal cord ischemia/reperfusion injury in rats. J Thorac Cardiovasc Surg, 133, 934-941.
- Nagar P, Sharma P, Dhapola R, et al (2023): Endoplasmic reticulum stress in Alzheimer's disease: Molecular mechanisms and therapeutic prospects. Life Sci, 121983.
- Paul BD, Pieper AA (2023): Protective Roles of Hydrogen Sulfide in Alzheimer’s Disease and Traumatic Brain Injury. Antioxidants, 12, 1095.
- Ryu JH, Kang D (2017): Physicochemical properties, biological activity, health benefits, and general limitations of aged black garlic: A review. Molecules, 22, 919.
- Sengul E, Gelen V, Yildirim S, et al (2023): Effects of naringin on oxidative stress, inflammation, some reproductive parameters, and apoptosis in acrylamide‐induced testis toxicity in rat. Environ Toxicol, 38, 798-808.
- Sun Y, Yu H, Guan Y (2023): Glia connect inflammation and neurodegeneration in multiple sclerosis. Neurosci Bull, 39, 466-478.
- Tedeschi P, Nigro M, Travagli A, et al (2022): Therapeutic potential of allicin and aged garlic extract in Alzheimer’s disease. Int J Mol Sci, 23, 6950.
- Thabet NM, Moustafa EM (2018): Protective effect of rutin against brain injury induced by acrylamide or gamma radiation: role of PI3K/AKT/GSK-3β/NRF-2 signalling pathway. Arch Physiol Biochem, 124, 185-193.
- Uluman E, Kilicle PA (2020): The investigation of the possible antigenotoxic in vivo effects of pomegranate (Punica granatum L.) peel extract on mitomycin-C genotoxicity. Turkish J Vet Anim Sci, 44, 382-390.
- Wang Y, Che M, Xin J, et al (2020): The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother, 131, 110660.
- White K (2023): Sayonara to some evolutionary puzzles in the Bcl‐2 family. EMBO J, 42, e113980.
- Yassa HA, George SM, Refaiy AERM, et al (2014): Camellia sinensis (green tea) extract attenuate acrylamide induced testicular damage in albino rats. Environ Toxicol, 29, 1155-1161.
- Yu D, Jiang X, Ge W, et al (2022): Gestational exposure to acrylamide suppresses luteal endocrine function through dysregulation of ovarian angiogenesis, oxidative stress, and apoptosis in mice. Food Chem Toxicol, 159, 112766.
- Yu S-M, Kim S-J (2015): The thymoquinone-induced production of reactive oxygen species promotes dedifferentiation through the ERK pathway and inflammation through the p38 and PI3K pathways in rabbit articular chondrocytes. Int J Mol Med, 35, 325-332.
- Zhang J, Zhu X, Xu W, et al (2023): Exposure to acrylamide inhibits testosterone production in mice testes and Leydig cells by activating ERK1/2 phosphorylation. Food Chem Toxicol, 172, 113576.
Year 2024,
, 395 - 406, 23.09.2024
Abstract
References
- Abdel-Daim MM, Abd Eldaim MA, Hassan AG (2015): Trigonella foenum-graecum ameliorates acrylamide-induced toxicity in rats: Roles of oxidative stress, proinflammatory cytokines, and DNA damage. Biochem Cell Biol, 93, 192-198.
- Ahmed RA (2018): Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide. JOBAZ, 79, 1-8.
- Ahmed T, Wang C-K (2021): Black garlic and its bioactive compounds on human health diseases: A review. Molecules, 26, 5028.
- Alizadeh M, Kheirouri S (2019): Curcumin reduces malondialdehyde and improves antioxidants in humans with diseased conditions: A comprehensive meta-analysis of randomized controlled trials. BioMedicine, 9.
- Al-Shehri SA (2021): Efficacy of black garlic extract on anti-tumor and anti-oxidant activity enhancement in rats. Clin Nutr Open Sci, 36, 126-139.
- Alturki HA, Elsawy HA, Famurewa AC (2022): Silymarin abrogates acrylamide‐induced oxidative stress‐mediated testicular toxicity via modulation of antioxidant mechanism, DNA damage, endocrine deficit and sperm quality in rats. Andrologia, 54, e14491.
- Aminuddin M, Partadiredja G, Sari D (2015): The effects of black garlic (Allium sativum L.) ethanol extract on the estimated total number of Purkinje cells and motor coordination of male adolescent Wistar rats treated with monosodium glutamate. Anat Sci Int, 90, 75-81.
- Aoudeh E, Oz E, Oz F (2023): Effect of beef patties fortification with black garlic on the polycyclic aromatic hydrocarbons (PAHs) content and toxic potency. Food Chem, 428, 136763.
- Begum SFM, Hemalatha S (2022): Gelidiella acerosa compounds target NFκB cascade in lung adenocarcinoma. Appl Biochem Biotechnol, 1-14.
- Chen Y, Zhang W, Guo X, et al (2019): The crosstalk between autophagy and apoptosis was mediated by phosphorylation of Bcl-2 and beclin1 in benzene-induced hematotoxicity. Cell Death Dis, 10, 772.
- Conti P, Ronconi G, Caraffa A, et al (2020): Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents, 34, 327-331.
- Edres HA, Taha NM, Lebda MA, et al (2021): The potential neuroprotective effect of allicin and melatonin in acrylamide-induced brain damage in rats. Environ Sci Pollut Res, 28, 58768-58780.
- Fang Z, Luo Y, Ma C (2022): Blueberry anthocyanins extract attenuates acrylamide-induced oxidative stress and neuroinflammation in rats. Oxid Med Cell Longev, 2022.
- Farag OM, Abd-Elsalam RM, El Badawy SA, et al (2021): Portulaca oleracea seeds’ extract alleviates acrylamide-induced testicular dysfunction by promoting oxidative status and steroidogenic pathway in rats. BMC Complement Altern Med, 21, 1-15.
- für Gesundheit HKBL (2023): Lebensmittel: Acrylamid.
- Gao J-G, Jiang Y, Zheng J-T, et al (2022): Pubertal exposure to acrylamide disrupts spermatogenesis by interfering with meiotic progression in male mice. Toxicol Lett, 358, 80-87.
- Gelen V, Özkanlar S, Kara A, et al (2023): Citrate-coated silver nanoparticles loaded with agomelatine provide neuronal therapy in acute cerebral ischemia/reperfusion of rats by inhibiting the oxidative stress, endoplasmic reticulum stress, and P2X7 receptor-mediated inflammasome. Environ Toxicol, 39, 1-13.
- Gelen V, Sengul E, Yildirim S, et al (2023): The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats. Iran J Basic Med Sci, 26, 1326-1333.
- Gelen V, Şengül E, Yıldırım S, et al (2021): The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice. Environ Sci Pollut Res, 28, 47046-47055.
- Gelen V, Yıldırım S, Şengül E, et al (2022): Naringin attenuates oxidative stress, inflammation, apoptosis, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats. Asian Pac J Trop Biomed, 12.
- Gezer A, Karadag-Sari E (2022): The role of amifostine in preventing radiotherapy-induced testicular tissue damage in rats. Biotech Histochem, 97, 215-221.
- Gezer A, Sari EK (2023): Investigation of apoptotic and autophagic effects of chronic roflumilast use on testicular tissue in rats by immunohistochemical and immunofluorescence methods. Iran J Basic Med Sci, 26, 276.
- Goudarzi M, Mombeini MA, Fatemi I, et al (2019): Neuroprotective effects of Ellagic acid against acrylamide-induced neurotoxicity in rats. Neurol Res, 41, 419-428.
- Gu X, Nardone C, Kamitaki N, et al (2023): The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation. Science, 381, eadh5021.
- Gur C, Kandemir FM, Darendelioglu E, et al (2021): Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways. Environ Sci Pollut Res, 28, 49808-49819.
- Hermawati E, Sari DCR, Partadiredja G (2015): The effects of black garlic ethanol extract on the spatial memory and estimated total number of pyramidal cells of the hippocampus of monosodium glutamate-exposed adolescent male Wistar rats. Anat Sci Int, 90, 275-286.
- Hosseini E, Farid Habibi M, Babri S, et al (2022): Maternal stress induced anxiety-like behavior exacerbated by electromagnetic fields radiation in female rats offspring. PLoS One, 23, 17-18.
- Huang S-L, Chang T-C, Sun N-K (2023): Curcumin reduces paclitaxel resistance in ovarian carcinoma cells by upregulating SNIP1 and inhibiting NFκB activity. Biochem Pharmacol, 212, 115581.
- Kacar S, Sahinturk V (2021): The protective agents used against acrylamide toxicity: An in vitro cell culture study-based review. Cell Journal (Yakhteh), 23, 367.
- Kayacan S, Sener L, Melikoglu G, et al (2018): Induction of apoptosis by Centaurea nerimaniae extract in HeLa and MDA-MB-231 cells by a caspase-3 pathway. Biotech Histochem, 93, 311-319.
- Khakha N, Khan H, Kaur A, et al (2023): Therapeutic implications of phosphorylation-and dephosphorylation-dependent factors of cAMP-response element-binding protein (CREB) in neurodegeneration. Pharmacol Rep, 1-14.
- Kim J-J, Kang Y-J, Shin S-A, et al (2016): Phlorofucofuroeckol improves glutamate-induced neurotoxicity through modulation of oxidative stress-mediated mitochondrial dysfunction in PC12 cells. PLoS One, 11, e0163433.
- Kunle-Alabi OT, Akindele OO, Odoh MI, et al (2017): Comparative effects of coconut water and N-Acetyl cysteine on the hypothalamo-pituitary-gonadal axis of male rats. Songklanakarin J Sci Technol, 39, 759-764.
- Li F, Kim MR (2019): Effect of aged garlic ethyl acetate extract on oxidative stress and cholinergic function of scopolamine-Induced cognitive impairment in mice. Prev Nutr Food Sc, 24, 165.
- Lu K, Cho C-L, Liang C-L, et al (2007): Inhibition of the MEK/ERK pathway reduces microglial activation and interleukin-1-beta expression in spinal cord ischemia/reperfusion injury in rats. J Thorac Cardiovasc Surg, 133, 934-941.
- Nagar P, Sharma P, Dhapola R, et al (2023): Endoplasmic reticulum stress in Alzheimer's disease: Molecular mechanisms and therapeutic prospects. Life Sci, 121983.
- Paul BD, Pieper AA (2023): Protective Roles of Hydrogen Sulfide in Alzheimer’s Disease and Traumatic Brain Injury. Antioxidants, 12, 1095.
- Ryu JH, Kang D (2017): Physicochemical properties, biological activity, health benefits, and general limitations of aged black garlic: A review. Molecules, 22, 919.
- Sengul E, Gelen V, Yildirim S, et al (2023): Effects of naringin on oxidative stress, inflammation, some reproductive parameters, and apoptosis in acrylamide‐induced testis toxicity in rat. Environ Toxicol, 38, 798-808.
- Sun Y, Yu H, Guan Y (2023): Glia connect inflammation and neurodegeneration in multiple sclerosis. Neurosci Bull, 39, 466-478.
- Tedeschi P, Nigro M, Travagli A, et al (2022): Therapeutic potential of allicin and aged garlic extract in Alzheimer’s disease. Int J Mol Sci, 23, 6950.
- Thabet NM, Moustafa EM (2018): Protective effect of rutin against brain injury induced by acrylamide or gamma radiation: role of PI3K/AKT/GSK-3β/NRF-2 signalling pathway. Arch Physiol Biochem, 124, 185-193.
- Uluman E, Kilicle PA (2020): The investigation of the possible antigenotoxic in vivo effects of pomegranate (Punica granatum L.) peel extract on mitomycin-C genotoxicity. Turkish J Vet Anim Sci, 44, 382-390.
- Wang Y, Che M, Xin J, et al (2020): The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother, 131, 110660.
- White K (2023): Sayonara to some evolutionary puzzles in the Bcl‐2 family. EMBO J, 42, e113980.
- Yassa HA, George SM, Refaiy AERM, et al (2014): Camellia sinensis (green tea) extract attenuate acrylamide induced testicular damage in albino rats. Environ Toxicol, 29, 1155-1161.
- Yu D, Jiang X, Ge W, et al (2022): Gestational exposure to acrylamide suppresses luteal endocrine function through dysregulation of ovarian angiogenesis, oxidative stress, and apoptosis in mice. Food Chem Toxicol, 159, 112766.
- Yu S-M, Kim S-J (2015): The thymoquinone-induced production of reactive oxygen species promotes dedifferentiation through the ERK pathway and inflammation through the p38 and PI3K pathways in rabbit articular chondrocytes. Int J Mol Med, 35, 325-332.
- Zhang J, Zhu X, Xu W, et al (2023): Exposure to acrylamide inhibits testosterone production in mice testes and Leydig cells by activating ERK1/2 phosphorylation. Food Chem Toxicol, 172, 113576.
There are 49 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Anatomy and Physiology, Veterinary Biochemistry, Veterinary Histology and Embryology, Veterinary Pathology |
| Journal Section | Research Article |
| Authors | |
| Early Pub Date | March 19, 2024 |
| Publication Date | September 23, 2024 |
| Submission Date | November 1, 2023 |
| Acceptance Date | February 19, 2024 |
| Published in Issue | Year 2024 |