The aim of this study was to investigate the effect of melatonin on oxidative stress and senescence marker protein-30 (SMP30) as well as osteopontin (OPN) expression in the hippocampus of rats subjected to vascular dementia (VD). A total of 72 male rats were divided into six groups (n = 12 each) as follows: (i) untreated control (CON), (ii) sham-operated group, (iii) sham-operated + melatonin, (iv) rats exposed to VD induced by permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (v) rats exposed to VD + melatonin, and (vi) rats exposed to VD + donepezil (DON). At the end of experiment, the hippocampal levels of acetylcholine (ACh), norepinephrine (NE), and dopamine (Dop) were measured. Expression of OPN was determined using immunohistochemistry, and SMP30 expression was determined using real-time PCR in the hippocampus. Hippocampal thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were evaluated. The BCCAO group showed significantly decreased TAC (p < 0.05) and significantly increased in TBARS levels compared with the CON group. In addition, BCCAO significantly decreased (p < 0.05) the expression of both OPN and SMP30 and the levels of ACh, NE, and Dop in the hippocampus compared with CON treatment. Treatment with melatonin significantly increased OPN and SMP30 expression and ACh, NE, and Dop levels in the hippocampus with amelioration of the oxidative stress compared with BCCAO rats. Melatonin might produce a neuroprotective effect through its antioxidant action and by increasing the expression of SMP30 and OPN that is not comparable with that of DON.
Ali T , Badshah H , Kim TH , Kim MO : Melatonin attenuates d-galactose-induced memory impairment, neuroinflammation and neurodegeneration via RAGE/NF-K B/JNK signaling pathway in aging mouse model. J. Pineal Res. 58, 71–85 (2015)
Ali T , Kim MO : Melatonin ameliorates amyloid beta-induced memory deficits, tau hyperphosphorylation and neurodegeneration via PI3/Akt/GSk3beta pathway in the mouse hippocampus. J. Pineal Res. 59, 47–59 (2015)
Arruda LF , Arruda SF , Campos NA , de Valencia FF , Siqueira EM : Dietary iron concentration may influence aging process by altering oxidative stress in tissues of adult rats. PLoS One 8, e61058 (2013)
Battistin L , Cagnin A : Vascular cognitive disorder. A biological and clinical overview. Neurochem. Res. 35, 1933–1938 (2010)
Birks J , Harvey RJ : Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst. Rev. 25, CD001190 (2006)
Butterfield DA , Lauderback CM : Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic. Biol. Med. 32, 1050–1060 (2002)
Cardinali DP , Nagle CA , Freire F , Rosner JM : Effects of melatonin on neurotransmitter uptake and release by synaptosome-rich homogenates of the rat hypothalamus. Neuroendocrinology 18, 72–85 (1975)
Chen SD , Lee JM , Yang DI , Nassief A , Hsu CY : Combination therapy for ischemic stroke: potential of neuroprotectants plus thrombolytics. Am. J. Cardiovasc. Drugs 2, 303–313 (2002)
Chen SD , Lin TK , Yang DI , Lee SY , Shaw FZ , Liou CW , Chuang YC : Protective effects of peroxisome proliferator-activated receptors gamma coactivator-1alpha against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia. J. Neurosci. Res. 88, 605–613 (2010)
Chen W , Ma Q , Suzuki H , Hartman R , Tang J , Zhang JH : Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model. Stroke 42, 764–769 (2011)
Das A , McDowell M , Pava MJ , Smith JA , Reiter RJ , Woodward JJ , Varma AK , Ray SK , Banik NL : The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-alpha toxicity involves membrane melatonin receptors. J. Pineal Res. 48, 157–169 (2010)
Du X , Chen L , Huang D , Peng Z , Zhao C , Zhang Y , Zhu Y , Wang Z , Li X , Liu G : Elevated apoptosis in the liver of dairy cows with ketosis. Cell. Physiol. Biochem. 43, 568–578 (2017)
Esteban S , Garau C , Aparicio S , Moranta D , Barcelo P , Fiol MA , Rial R : Chronic melatonin treatment and its precursor l-tryptophan improve the monoaminergic neurotransmission and related behavior in the aged rat brain. J. Pineal Res. 48, 170–177 (2010)
Feng Z , Cheng Y , Zhang JT : Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats. J. Pineal Res. 37, 198–206 (2004)
Gutierrez-Cuesta J , Tajes M , Jimenez A , Camins A , Pallas M : Effects of melatonin in the brain of the senescence-accelerated mice-prone 8 (SAMP8) model. Rev. Neurol. 52, 618–622 (2011)
Hashimoto M , Koda M , Ino H , Murakami M , Yamazaki M , Moriya H : Upregulation of osteopontin expression in rat spinal cord microglia after traumatic injury. J. Neurotrauma 20, 287–296 (2003)
Huang Q , Dunn RT 2nd , Jayadev S , DiSorbo O , Pack FD , Farr SB , Stoll RE , Blanchard KT : Assessment of cisplatin-induced nephrotoxicity by microarray technology. Toxicol. Sci. 63, 196–207 (2001)
Hudkins KL , Giachelli CM , Cui Y , Couser WG , Johnson RJ , Alpers CE : Osteopontin expression in fetal and mature human kidney. J. Am. Soc. Nephrol. 10, 444–457 (1999)
Ishigami A , Handa S , Maruyama N , Supakar PC : Nuclear localization of senescence marker protein-30, SMP30, in cultured mouse hepatocytes and its similarity to RNA polymerase. Biosci. Biotechnol. Biochem. 67, 158–160 (2003)
Katalinic V , Modun D , Music I , Boban M : Gender differences in antioxidant capacity of rat tissues determined by 2,2′-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 140, 47–52 (2005)
Kim SY , Choi YS , Choi JS , Cha JH , Kim ON , Lee SB , Chung JW , Chun MH , Lee MY : Osteopontin in kainic acid-induced microglial reactions in the rat brain. Mol. Cells 13, 429–435 (2002)
Li DD , Luo Z , Chen GH , Song YF , Wei CC , Pan YX : Identification of apoptosis-related genes Bcl2 and Bax from yellow catfish Pelteobagrus fulvidraco and their transcriptional responses to waterborne and dietborne zinc exposure. Gene 633, 1–8 (2017)
Li GY , Xie P , Li HY , Hao L , Xiong Q , Qiu T : Involment of p53, Bax, and Bcl-2 pathway in microcystins-induced apoptosis in rat testis. Environ. Toxicol. 26, 111–117 (2011)
Malhotra S , Sawhney G , Pandhi P : The therapeutic potential of melatonin: a review of the science. MedGenMed. 6, 46 (2004)
Manchester LC , Coto-Montes A , Boga JA , Andersen LP , Zhou Z , Galano A , Vriend J , Tan DX , Reiter RJ : Melatonin: an ancient molecule that makes oxygen metabolically tolerable. J. Pineal Res. 59, 403–419 (2015)
Mauriz JL , Collado PS , Veneroso C , Reiter RJ , Gonzalez-Gallego J : A review of the molecular aspects of melatonin’s anti-inflammatory actions: recent insights and new perspectives. J. Pineal Res. 54, 1–14 (2013)
Mazzali M , Kipari T , Ophascharoensuk V , Wesson JA , Johnson R , Hughes J : Osteopontin – a molecule for all seasons. QJM 95, 3–13 (2002)
Meller R , Stevens SL , Minami M , Cameron JA , King S , Rosenzweig H , Doyle K , Lessov NS , Simon RP , Stenzel-Poore MP : Neuroprotection by osteopontin in stroke. J. Cereb. Blood Flow Metab. 25, 217–225 (2005)
Meyer JS , Rauch G , Rauch RA , Haque A : Risk factors for cerebral hypoperfusion, mild cognitive impairment, and dementia. Neurobiol. Aging 21, 161–169 (2000)
Miyata M , Suzuki S , Misaka T , Shishido T , Saitoh S , Ishigami A , Kubota I , Takeishi Y : Senescence marker protein 30 has a cardio-protective role in doxorubicin-induced cardiac dysfunction. PLoS One 8, e79093 (2013)
Niizuma K , Endo H , Chan PH : Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival. J. Neurochem. 1, 133–138 (2009)
Pakaski M , Feher A , Juhasz A , Drotos G , Fazekas OC , Kovacs J , Janka Z , Kalman J : Serum adipokine levels modified by donepezil treatment in Alzheimer’s disease. J. Alzheimers Dis. 38, 371–377 (2014)
Parada E , Buendia I , Leon R , Negredo P , Romero A , Cuadrado A , Lopez MG , Egea J : Neuroprotective effect of melatonin against ischemia is partially mediated by alpha-7 nicotinic receptor modulation and HO-1 overexpression. J. Pineal Res. 56, 204–212 (2014)
Reiter RJ , Mayo JC , Tan DX , Sainz RM , Alatorre-Jimenez M , Qin L : Melatonin as an antioxidant: under promises but over delivers. J. Pineal Res. 61, 253–278 (2016)
Reiter RJ , Tan DX , Leon J , Kilic U , Kilic E : When melatonin gets on your nerves: its beneficial actions in experimental models of stroke. Exp. Biol. Med. 230, 104–117 (2005)
Reiter RJ , Tan DX , Manchester LC , Qi W : Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem. Biophys. 34, 237–256 (2001)
Romuk EB , Szczurek W , Oles M , Gabrysiak A , Skowron M , Nowak P , Birkner E : The evaluation of the changes in enzymatic antioxidant reserves and lipid peroxidation in chosen parts of the brain in an animal model of Parkinson disease. Adv. Clin. Exp. Med. 26, 953–959 (2017)
Rosales-Corral SA , Acuna-Castroviejo D , Coto-Montes A , Boga JA , Manchester LC , Fuentes-Broto L , Korkmaz A , Ma S , Tan DX , Reiter RJ : Alzheimer’s disease: pathological mechanisms and the beneficial role of melatonin. J. Pineal Res. 52, 167–202 (2012)
Roth JA , Kim BG , Lin WL , Cho MI : Melatonin promotes osteoblast differentiation and bone formation. J. Biol. Chem. 274, 22041–22047 (1999)
Sakr HF , Abbas AM , Bin-Jaliah I : Modulation of the neurological and vascular complications by grape seed extract in a rat model of spinal cord ischemia-reperfusion injury by downregulation of both osteopontin and cyclooxygenase-2. Can. J. Physiol. Pharmacol. 94, 719–727 (2016)
Sakr HF , Abbas AM , Elsamanoudy AZ : Effect of valsartan on cardiac senescence and apoptosis in a rat model of cardiotoxicity. Can. J. Physiol. Pharmacol. 94, 588–598 (2016)
Sakr HF , Al-Ani B : Modulation of proinflammatory cytokines and leukocyte mobilization by melatonin in response to sterile tissue injury in Wistar albino rats. Saudi Med. J. 34, 470–476 (2013)
Sakr HF , Khalil KI , Hussein AM , Zaki MS , Eid RA , Alkhateeb M : Effect of dehydroepiandrosterone (DHEA) on memory and brain derived neurotrophic factor (BDNF) in a rat model of vascular dementia. J. Physiol. Pharmacol. 65, 41–53 (2014)
Santana Pereira JA , de Haan A , Wessels A , Moorman AF , Sargeant AJ : The mATPase histochemical profile of rat type IIX fibres: correlation with myosin heavy chain immunolabelling. Histochem. J. 27, 715–722 (1995)
Sato Y , Kajiyama S , Amano A , Kondo Y , Sasaki T , Handa S , Takahashi R , Fukui M , Hasegawa G , Nakamura N , Fujinawa H , Mori T , Ohta M , Obayashi H , Maruyama N , Ishigami A : Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem. Biophys. Res. Commun. 375, 346–350 (2008)
Son TG , Zou Y , Jung KJ , Yu BP , Ishigami A , Maruyama N , Lee J : SMP30 deficiency causes increased oxidative stress in brain. Mech. Ageing Dev. 127, 451–457 (2006)
Stasiak A , Mussur M , Unzeta M , Lazewska D , Kiec-Kononowicz K , Fogel WA : The central histamine level in rat model of vascular dementia. J. Physiol. Pharmacol. 62, 549–558 (2011)
Sun H , Zhang J , Zhang L , Liu H , Zhu H , Yang Y : Environmental enrichment influences BDNF and NR1 levels in the hippocampus and restores cognitive impairment in chronic cerebral hypoperfused rats. Curr. Neurovasc. Res. 7, 268–280 (2010)
Suzuki H , Ayer R , Sugawara T , Chen W , Sozen T , Hasegawa Y , Kanamaru K , Zhang JH : Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats. Crit. Care Med. 38, 612–618 (2010)
Tachibana R , Tatehara S , Kumasaka S , Tokuyama R , Satomura K : Effect of melatonin on human dental papilla cells. Int. J. Mol. Sci. 15, 17304–17317 (2014)
Wang Q , Du F , Qian ZM , Ge XH , Zhu L , Yung WH , Yang L , Ke Y : Lipopolysaccharide induces a significant increase in expression of iron regulatory hormone hepcidin in the cortex and substantia nigra in rat brain. Endocrinology 149, 3920–3925 (2008)
Yang Y , Jiang S , Dong Y , Fan C , Zhao L , Yang X , Li J , Di S , Yue L , Liang G , Reiter RJ , Qu Y : Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice. J. Pineal Res. 58, 61–70 (2015)
Yoshioka T , Kawada K , Shimada T , Mori M : Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am. J. Obstet. Gynecol. 135, 372–376 (1979)
Yuan J : Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke. Apoptosis 14, 469–477 (2009)
Yun SP , Han YS , Lee JH , Kim SM , Lee SH : Melatonin rescues mesenchymal stem cells from senescence induced by the uremic toxin p-cresol via inhibiting mTOR-dependent autophagy. Biomol. Ther. (Seoul) 27, 1–10 (2017). doi:10.4062/biomolther.2017.071
Zhang HM , Zhang Y : Melatonin: a well-documented antioxidant with conditional pro-oxidant actions. J. Pineal Res. 57, 131–146 (2014)