Winer N, Sowers JR. Epidemiology of diabetes. J Clin Pharmacol. 2004;44:397–405.
Article
PubMed
Google Scholar
International Diabetes Federation. 2017. IDF Atlas, 8th Edn. https://www.idf.org/component/attachments/attachments.html?id=1405&task=download. Accessed 9 Jan 2019.
Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012;5:9–19.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother. 2005;59:365–73.
Article
CAS
PubMed
Google Scholar
Elbe H, Vardi N, Esrefoglu M, Ates B, Yologlu S, Taskapan C. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin and resveratrol in rats. Hum Exp Toxicol. 2015;34:100–13.
Article
CAS
PubMed
Google Scholar
Hu XZ, Xing XH, Zhang ZM, Wu RQ, Guo Q, Cui SW, et al. Antioxidant effects of Artemis sphaerocephala Krasch. gum, on streptozotocin-induced type 2 diabetic rats. Food Hydrocoll. 2011;25:207–13.
Article
CAS
Google Scholar
Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res. 2005;19:997–1000.
Article
CAS
PubMed
Google Scholar
Altinoz E, Oner Z, Elbe H, Vardi N. Neuro-protective effects of crocin on brain and cerebellum tissues in diabetic rats. Afr J Tradit Complement Altern Med. 2014;11:33–9.
Article
Google Scholar
Correia MLG, Haynes WG. A role for plasminogen activator inhibitor-1 in obesity: from pie to PAI? Arterioscler Thromb Vasc Biol. 2006;26:2183–5.
Article
CAS
PubMed
Google Scholar
Tsuda T, Ueno Y, Yoshikawa T, Kojo H, Osawa T. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochem Pharmacol. 2006;71:1184–97.
Article
CAS
PubMed
Google Scholar
Belalcazar LM, Ballantyne CM, Lang W, Haffner SM, Rushing J, Schwenke DC, et al. Metabolic factors, adipose tissue, and Plasminogen Activator Inhibitor-1 levels in type 2 diabetes: findings from the Look AHEAD study. Arterioscler Thromb Vasc Biol. 2011;31:1689–95.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tsantarliotou MP, Lavrentiadou SN, Psalla DA, Margaritis IE, Kritsepi MG, Zervos IA, et al. Suppression of plasminogen activator inhibitor-1 (PAI-1) activity by crocin ameliorates lipopolysaccharide-induced thrombosis in rats. Food Chem Toxicol. 2019;125:190–7.
Article
CAS
PubMed
Google Scholar
Feidantsis K, Mellidis K, Galatou E, Sinakos Z, Lazou A. Treatment with crocin improves cardiac dysfunction by normalizing autophagy and inhibiting apoptosis in STZ-induced diabetic cardiomyopathy. Nutr Metab Cardiovasc Dis. 2018;28:952–61.
Article
CAS
PubMed
Google Scholar
Altinoz E, Oner Z, Elbe H, Turkoz Y, Cigremis Y. Protective effect of saffron (its active constituent, crocin) on oxidative stress and hepatic injury in streptozotocin induced diabetic rats. Gene Ther Mol Biol. 2014;16:160–71.
Google Scholar
Altinoz E, Oner Z, Elbe H, Cigremis Y, Turkoz Y. Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats. Hum Exp Toxicol. 2015;34:127–34.
Article
CAS
PubMed
Google Scholar
Abou-Hany HO, Atef H, Said E, Elkashef HA, Salem HA. Crocin mediated amelioration of oxidative burden and inflammatory cascade suppresses diabetic nephropathy progression in diabetic rats. Chem Biol Interact. 2018;284:90–100.
Article
CAS
PubMed
Google Scholar
Tamaddonfard E, Farshid AA, Asri-Rezaee S, Javadi S, Khosravi V, Rahman B, et al. Crocin improved learning and memory impairments in streptozotocin-induced diabetic rats. Iran J Basic Med Sci. 2013;16:91–100.
PubMed
PubMed Central
Google Scholar
Arasteh A, Aliyev A, Khamnei S, Delazar A, Mesgari M, Mehmannavaz Y. Effects of hydromethanolic extract of saffron (Crocus sativus) on serum glucose, insulin and cholesterol levels in healthy male rats. J Med Plants Res. 2010;4:397–402.
Google Scholar
Asai A, Nakano T, Takahashi M, Nagao A. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J Agric Food Chem. 2005;53:7302–6.
Article
CAS
PubMed
Google Scholar
Sheng L, Qian Z, Zheng S, Xi L. Mechanism of hypolipidemic effect of crocin in rats: crocin inhibits pancreatic lipase. Eur J Pharmacol. 2006;543:116–22.
Article
CAS
PubMed
Google Scholar
Hazman Ö, Aksoy L, Büyükben A. Effects of crocin on experimental obesity and type-2 diabetes. Turk J Med Sci. 2016;46:1593–602.
Article
CAS
PubMed
Google Scholar
Mashmoul M, Azlan A, Yusof BNM, Khaza’ai H, Mohtarrudin N, Boroushaki MT. Effects of saffron extract and crocin on anthropometrical, nutritional and lipid profile parameters of rats fed a high fat diet. J Funct Foods. 2014;8:180–7.
Article
CAS
Google Scholar
Magesh V, Singh JP, Selvendiran K, Ekambaram G, Sakthisekaran D. Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies. Mol Cell Biochem. 2006;287:127–35.
Article
CAS
PubMed
Google Scholar
Rahbani M, Mohajeri D, Rezaie A, Doustar Y, Nazeri M. Attenuation of oxidative stress of hepatic tissue by ethanolic extract of saffron (dried stigmas of Crocus sativus L.) in streptozotocin (STZ)-induced diabetic rats. Afr J Pharm Pharmacol. 2011;5:2166–73.
Google Scholar
Maritim AC, Sanders RA, Watkins JB 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17:24–38.
Article
CAS
PubMed
Google Scholar
Boussabbeh M, Ben Salem I, Belguesmi F, Bacha H, Abid-Essefi S. Tissue oxidative stress induced by patulin and protective effect of crocin. Neurotoxicology. 2016;53:343–9.
Article
CAS
PubMed
Google Scholar
Bouayed J, Bohn T. Exogenous antioxidants—Double-edged swords in cellular redox state: health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid Med Cell Longev. 2010;3:228–37.
Article
PubMed
PubMed Central
Google Scholar
Kakkar R, Mantha SV, Radhi J, Prasad K, Kalra J. Antioxidant defense system in diabetic kidney: a time course study. Life Sci. 1997;60:667–79.
Article
CAS
PubMed
Google Scholar
Wang G, Xiu P, Li F, Xin C, Li K. Vitamin A supplementation alleviates extrahepatic cholestasis liver injury through Nrf2 activation. Oxid Med Cell Longev. 2014;2014:273692.
PubMed
PubMed Central
Google Scholar
Maritim AC, Moore BH, Sanders RA, Watkins JB 3rd. Effects of melatonin on oxidative stress in streptozotocin-induced diabetic rats. Int J Toxicol. 1999;18:161–6.
Article
CAS
Google Scholar
Bandegi AR, Rashidy-Pour A, Vafaei AA, Ghadrdoost B. Protective effects of Crocus sativus L. Extract and crocin against chronic-stress induced oxidative damage of brain, liver and kidneys in rats. Adv Pharm Bull. 2014;4(Suppl 2):493–9.
PubMed
PubMed Central
Google Scholar
Kataya HA, Hamza AA. Red cabbage (Brassica oleracea) ameliorates diabetic nephropathy in rats. Evid Based Complement Alternat Med. 2008;5:281–7.
Article
PubMed
Google Scholar
El-Beshbishy HA, Hassan MH, Aly HA, Doghish AS, Alghaithy AA. Crocin “saffron” protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes. Ecotoxicol Environ Saf. 2012;83:47–54.
Article
CAS
PubMed
Google Scholar
Palsamy P, Subramanian S. Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2–Keap1 signaling. Biochim Biophys Acta. 2011;1812:719–31.
Article
CAS
PubMed
Google Scholar
Chiş IC, Mureşan A, Oros A, Nagy AL, Clichici S. Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats. Physiol Int. 2016;103:49–64.
PubMed
Google Scholar
Meena S, Rajput YS, Pandey AK, Sharma R, Singh R. Camel milk ameliorates hyperglycaemia and oxidative damage in type-1 diabetic experimental rats. J Dairy Res. 2016;83:412–9.
Article
CAS
PubMed
Google Scholar
Gedik S, Erdemli ME, Gul M, Yigitcan B, Gozukara Bag H, Aksungur Z, et al. Hepatoprotective effects of crocin on biochemical and histopathological alterations following acrylamide-induced liver injury in Wistar rats. Biomed Pharmacother. 2017;95:764–70.
Article
CAS
PubMed
Google Scholar
Ochiai T, Soeda S, Ohno S, Tanaka H, Shoyama Y, Shimeno H. Crocin prevents the death of PC-12 cells through sphingomyelinase-ceramide signaling by increasing glutathione synthesis. Neurochem Int. 2004;44:321–30.
Article
CAS
PubMed
Google Scholar
Skrzydlewska E, Ostrowska J, Farbiszewski R, Michalak K. Protective effect of green tea against lipid peroxidation in the rat liver, blood serum and the brain. Phytomedicine. 2002;9:232–8.
Article
CAS
PubMed
Google Scholar
Papadopoulou A, Petrotos K, Stagos D, Gerasopoulos K, Maimaris A, Makris H, et al. Enhancement of antioxidant mechanisms and reduction of oxidative stress in chickens after the administration of drinking water enriched with polyphenolic powder from olive mill waste waters. Oxid Med Cell Longev. 2017;2017:8273160.
Article
CAS
PubMed
PubMed Central
Google Scholar
Yuan L, Liu J, Zhen J, Xu Y, Chen S, Halm-Lutterodt NV, et al. Vegetable and fruit juice enhances antioxidant capacity and regulates antioxidant gene expression in rat liver, brain and colon. Genet Mol Biol. 2017;40:134–41.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bartosz G. Total antioxidant capacity. Adv Clin Chem. 2003;37:219–92.
Article
CAS
PubMed
Google Scholar
Hosseini SS, Jalili M, Panahi M, Naghilou Z, Dezhahang M. The effect of aerobic exercise and saffron supplementation on antioxidant capacity in diabetic rats. Int J Biosci. 2014;4:1–7.
Google Scholar
Nasiri A, Ziamajidi N, Abbasalipourkabir R, Goodarzi MT, Saidijam M, Behrouj H, et al. Beneficial effect of aqueous garlic extract on inflammation and oxidative stress status in the kidneys of type 1 diabetic rats. Indian J Clin Biochem. 2017;32:329–36.
Article
CAS
PubMed
Google Scholar
Karamouzis I, Sarafidis PA, Karamouzis M, Iliadis S, Haidich AB, Sioulis A, et al. Increase in oxidative stress but not in antioxidant capacity with advancing stages of chronic kidney disease. Am J Nephrol. 2008;28:397–404.
Article
CAS
PubMed
Google Scholar
Kusano C, Ferrari B. Total antioxidant capacity: a biomarker in biomedical and nutritional studies. J Cell Mol Biol. 2008;7:1–15.
CAS
Google Scholar
Nishikawa M, Hashida M, Takakura Y. Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis. Adv Drug Deliv Rev. 2009;61:319–26.
Article
CAS
PubMed
Google Scholar
Ahmed AA, Fedail JS, Musa HH, Kamboh AA, Sifaldin AZ, Musa TH. Gum Arabic extracts protect against hepatic oxidative stress in alloxan induced diabetes in rats. Pathophysiology. 2015;22:189–94.
Article
CAS
PubMed
Google Scholar
Sadi G, Yilmaz O, Güray T. Effect of vitamin C and lipoic acid on streptozotocin-induced diabetes gene expression: mRNA and protein expressions of Cu–Zn SOD and catalase. Mol Cell Biochem. 2008;309:109–16.
Article
CAS
PubMed
Google Scholar
Sadi G, Baloğlu MC, Pektaş MB. Differential gene expression in liver tissues of streptozotocin-induced diabetic rats in response to resveratrol treatment. PLoS ONE. 2015;10:e0124968.
Article
CAS
PubMed
PubMed Central
Google Scholar
Oliveras-López MJ, Berná G, Carneiro EM, López-García de la Serrana H, Martín F, López MC. An extra-virgin olive oil rich in polyphenolic compounds has antioxidant effects in OF1 mice. J Nutr. 2008;138:1074–8.
Article
PubMed
Google Scholar
Sadi G, Güray T. Gene expressions of Mn-SOD and GPx-1 in streptozotocin-induced diabetes: effect of antioxidants. Mol Cell Biochem. 2009;327:127–34.
Article
CAS
PubMed
Google Scholar
Lemkes BA, Hermanides J, Devries JH, Holleman F, Meijers JC, Hoekstra JB. Hyperglycemia: a prothrombotic factor? J Thromb Haemost. 2010;8:1663–9.
Article
CAS
PubMed
Google Scholar
Kearney K, Tomlinson D, Smith K, Ajjan R. Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk. Cardiovasc Diabetol. 2017;16:34.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dimova EY, Kietzmann T. Metabolic, hormonal and environmental regulation of plasminogen activator inhibitor-1 (PAI-1) expression: lessons from the liver. Thromb Haemost. 2008;100:992–1006.
Article
CAS
PubMed
Google Scholar
Min AK, Kim MK, Seo HY, Kim HS, Jang BK, Hwang JS, et al. Alpha-lipoic acid inhibits hepatic PAI-1 expression and fibrosis by inhibiting the TGF-β signaling pathway. Biochem Biophys Res Commun. 2010;393:536–41.
Article
CAS
PubMed
Google Scholar
Lawrence DA, Olson ST, Palaniappan S, Ginsburg D. Engineering plasminogen activator inhibitor 1 mutants with increased functional stability. Biochemistry. 1994;33:3643–8.
Article
CAS
PubMed
Google Scholar
Jokaji H, Asakura H, Saito M, Uotani C, Kumabashiri I, Morishita E, et al. Tissue-type plasminogen activator and its inhibitor (PAI-1) in plasma in cases of non-insulin-dependent diabetes mellitus (NIDDM). Nippon Ronen Igakkai Zasshi. 1990;27:699–705.
Article
CAS
PubMed
Google Scholar
Chan KC, Pen PJ, Yin MC. Anticoagulatory and antiinflammatory effects of astaxanthin in diabetic rats. J Food Sci. 2012;77:H76–80.
Article
CAS
PubMed
Google Scholar
Lee HB, Ha H. Plasminogen activator inhibitor-1 and diabetic nephropathy. Nephrology (Carlton). 2005;10:S11–3.
Article
CAS
PubMed
Google Scholar
Fisher EJ, McLennan SV, Yue DK, Turtle JR. High glucose reduces generation of plasmin activity by mesangial cells. Microvasc Res. 1997;53:173–8.
Article
CAS
PubMed
Google Scholar
Zhang J, Gu C, Lawrence DA, Cheung AK, Huang Y. A plasminogen activator inhibitor type 1 mutant retards diabetic nephropathy in db/db mice by protecting podocytes. Exp Physiol. 2014;99:802–15.
Article
CAS
PubMed
PubMed Central
Google Scholar
Asdaq SMB, Inamdar MN. Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats. Appl Biochem Biotechnol. 2010;162:358–72.
Article
CAS
PubMed
Google Scholar
Djordjevic B, Baralic I, Kotur-Stevuljevic J, Stefanovic A, Ivanisevic J, Radivojevic N, et al. Effect of astaxanthin supplementation on muscle damage and oxidative stress markers in elite young soccer players. J Sports Med Phys Fitness. 2012;52:382–92.
CAS
PubMed
Google Scholar
Kianbakht S, Hajiaghaee R. Anti-hyperglycemic effects of saffron and its active constituents, crocin and safranal, in alloxan-induced diabetic rats. J Med Plants. 2011;10:82–9.
CAS
Google Scholar
Kulina GR, Rayfield EJ. The role of glucagon in the pathophysiology and management of diabetes. Endocr Pract. 2016;22:612–21.
Article
PubMed
Google Scholar
Herdt TH, Sayegh AI. Postabsorptive nutrient utilization. In: Klein B, editor. Cunningham’s textbook of veterinary physiology. 5th ed. St Louis: Elsevier; 2013. p. 352–3.
Google Scholar
Park NY, Park SK, Lim Y. Long-term dietary antioxidant cocktail supplementation effectively reduces renal inflammation in diabetic mice. Br J Nutr. 2011;106:1514–21.
Article
CAS
PubMed
Google Scholar
Ravarotto V, Simioni F, Pagnin E, Davis PA, Calò LA. Oxidative stress—chronic kidney disease—cardiovascular disease: a vicious circle. Life Sci. 2018;210:125–31.
Article
CAS
PubMed
Google Scholar
Dabla PK. Renal function in diabetic nephropathy. World J Diabetes. 2010;1:48–56.
Article
PubMed
PubMed Central
Google Scholar
Garcia-Olmo DC, Riese HH, Escribano J, Ontanon J, Fernandez JA, Atiénzar M, et al. Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat. Nutr Cancer. 1999;35:120–6.
Article
CAS
PubMed
Google Scholar
Hariri AT, Moallem SA, Mahmoudi M, Memar B, Hosseinzadeh H. Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: protective effects of crocin and safranal. Food Chem Toxicol. 2010;48:2803–8.
Article
CAS
PubMed
Google Scholar
Mohamadpour AH, Ayati Z, Parizadeh MR, Rajbai O, Hosseinzadeh H. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci. 2013;16:39–46.
PubMed
PubMed Central
Google Scholar
Young NL, Lopez D, McNamara D. Contributions of absorbed dietary cholesterol and cholesterol synthesized in small intestine to hypercholesterolemia in diabetic rats. Diabetes. 1988;37:1151–6.
Article
CAS
PubMed
Google Scholar
Altinoz E, Taskin E, Oner Z, Elbe H, Arslan BA. The effect of saffron (its active constituent, crocin) on the cardiovascular complication and dyslipidemia in streptozotocin induced diabetic rats. Afr J Tradit Complement Altern Med. 2015;12:1–7.
Article
CAS
Google Scholar
Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, et al. Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes. 1998;47:224–9.
Article
CAS
PubMed
Google Scholar
Jangale NM, Devarshi PP, Dubal AA, Ghule AE, Koppikar SJ, Bodhankar SL, et al. Dietary flaxseed oil and fish oil modulates expression of antioxidant and inflammatory genes with alleviation of protein glycation status and inflammation in liver of streptozotocin-nicotinamide induced diabetic rats. Food Chem. 2013;141:187–95.
Article
CAS
PubMed
Google Scholar
Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51:216–26.
Article
CAS
PubMed
Google Scholar
Oishi K, Ohkura N. Strain- and tissue-dependent induction of plasminogen activator inhibitor-1 gene expression in fasted mice. Biol Pharm Bull. 2010;33:530–1.
Article
CAS
PubMed
Google Scholar
Tsimidou M, Tsatsaroni E. Stability of saffron pigments in aqueous extracts. J Food Sci. 1993;58:1073–5.
Article
CAS
Google Scholar
Lee YM, Song BC, Yeum KJ. Impact of volatile anesthetics on oxidative stress and inflammation. Biomed Res Int. 2015;2015:242709.
PubMed
PubMed Central
Google Scholar
Veskoukis AS, Kyparos A, Nikolaidis MG, Stagos D, Aligiannis N, Halabalaki M, et al. The antioxidant effects of a polyphenol-rich grape pomace extract in vitro do not correspond in vivo using exercise as an oxidant stimulus. Oxid Med Cell Longev. 2012;2012:185867.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lubos E, Loscalzo J, Handy DE. Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxidants Redox Signal. 2011;15:1957–97.
Article
CAS
Google Scholar
Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–6.
Article
CAS
PubMed
Google Scholar
Veskoukis AS, Kyparos A, Paschalis V, Nikolaidis MG. Spectrophotometric assays for measuring redox biomarkers in blood. Biomarkers. 2016;21:208–17.
Article
CAS
PubMed
Google Scholar
Aureliano M, Joaquim N, Sousa A, Martins H, Coucelo JM. Oxidative stress in toadfish (Halobactrachus didactylus) cardiac muscle. Acute exposure to vanadate oligomers. J Inorg Biochem. 2002;90:159–65.
Article
CAS
PubMed
Google Scholar
Janaszewska A, Bartosz G. Assay of total antioxidant capacity: comparison of four methods as applied to human blood plasma. Scand J Clin Lab Invest. 2002;62:231–6.
Article
CAS
PubMed
Google Scholar
Patsoukis N, Zervoudakis G, Panagopoulos NT, Georgiou CD, Angelatou F, Matsokis NA. Thiol redox state (TRS) and oxidative stress in the mouse hippocampus after pentylenetetrazol-induced epileptic seizure. Neurosci Lett. 2004;357:83–6.
Article
CAS
PubMed
Google Scholar
Reddy YN, Murthy SV, Krishna DR, Prabhakar MC. Role of free radicals and antioxidants in tuberculosis patients. Indian J Tuberc. 2004;51:213–8.
Google Scholar
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.
Article
CAS
PubMed
Google Scholar
Koressaar T, Lepamets M, Kaplinski L, Raime K, Andreson R, Remm M. Primer3_masker: integrating masking of template sequence with primer design software. Bioinformatics. 2018;34:1937–8.
Article
CAS
PubMed
Google Scholar
Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45.
Article
CAS
PubMed
PubMed Central
Google Scholar