Crocin, a dietary colorant mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines

Jnaneshwari, S.; Hemshekhar, Mahadevappa; Santhosh, M. Sebastin; Sunitha, K.; Thushara, R. M.; Thirunavukkarasu, Chinnasamy; Kemparaju, K.; Girish, K. S.

doi:10.1111/jphp.12016

Cited by 70 publications

(45 citation statements)

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“…Nowadays, increased rates of cure or remission obtained by anticancer treatments (29,30) @ C I C E d i z i o n i I n t e r n a z i o n a l i fects on numerous cancer types including those with high incidence in women of reproductive age, they may represent good candidates as protective compounds against chemo-induced gonadotoxicity (21,31). In this context, present findings represent the first evidence for the chemoprotective potential of natural antioxidant compounds against ovarian cytotoxicity and are consistent with previous results in the male gonad and other organs in mice (21,32,33). It is known that PFs are in a quiescent state by fine tuning of the PI3K/PTEN/Akt-FOXO3a pathway (17).…”

Section: Discussionsupporting

confidence: 80%

Fertility preservation in cancer patients: attenuation of chemotherapy-induced ovarian damage by oral administration of phytochemical carotenoids in an animal model

Tatone¹

2015

CCE

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SummaryWe investigated the protective effects of a phytochemical carotenoid-rich extract obtained from Crocus sativus L., commonly known as saffron, against ovarian damage induced by cyclophosphamide (CPM). Mice received saffron extract (SE; 300 mg/kg) by oral administration for 15 days, followed by CPM treatment (100 mg/kg; SE+CPM group). The number of primordial and antral follicles decreased in CPM-mice when compared with control (p<0.001), whereas saffron administration prior to CPM partially prevented this loss. Protein expression of FOXO3a, a regulator of primordial follicle dormancy and adaptive response to oxidative stress, decreased in CPM-mice (p<0.05), whereas it was similar to control in the SE+CPM group (p=0.419). Levels of AGEs (Advanced-Glycation End-products), markers of oxidative stress and aging, were higher in CPM when compared to both control (p<0.05) and SE+CPM (p<0.05). Staining level for DNA double strand breaks increased in CPM ovaries (p<0.05), while it was similar to control in SE+CPM (p=0.194). These results provide evidence that oral administration of phytochemical carotenoids may counteract chemo-induced primordial follicle loss and oxidative damage. This approach may represent a pharmacological intervention to reduce the toxicity of alkylating agents so expanding options for fertility preservation in cancer patients.KEY WORDS:cyclophosphamide (CPM), premature ovarian failure (POF), saffron extract, oxidative stress, FOXO3a.

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Section: Discussionsupporting

confidence: 80%

Fertility preservation in cancer patients: attenuation of chemotherapy-induced ovarian damage by oral administration of phytochemical carotenoids in an animal model

Tatone¹

2015

CCE

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“…It was observed that there is an significant rise in the level of TAC with administered CYP plus HT. These may imply that overproduction of reactive oxygen species could be reduced by the HT, in the same line, other studies indicated a decrease in the antioxidantive enzyme activity is a consequence of raised oxidative stress in the heart tissue [34,37]. This results are consistent with numerous researches [11,16,38].…”

Section: Tocsupporting

confidence: 82%

“…The GSH level was found significantly increased in the 25, 50, 100 mg/kg HT-administered groups compared with group of CYP. In the same line it was observed that HT following CYP treatment protected the normal GSH level [34]. Paralel to our results, Liu et al [25] demonstrated the highest MDA level and the lowest GSH level in the CYP group compared to control.…”

Section: Tocsupporting

confidence: 77%

“…It was demonstrated in the experimental study that CYP administration led to oxidative stress measured as MDA concentration as the indicator of lipid peroxidation [33]. As it's seen in the figure 4, MDA level was remarkably high in the CYP-treated group compared to control [34,25]. HT doses, specially in the 50 mg/kg CYP+HT significantly inhibited the increase in MDA level.…”

Section: Tocmentioning

confidence: 79%

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Cardioprotective effects of Hypericum triquetrifolium Turra. against cyclophosphamide related cardiotoxicity in rats

Yıldız¹,

Keskin²,

Şahıntürk³

et al. 2018

jrp

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Cyclophosphamide (CYP) is commonly used as anticancer agent but its usage is limited by cardiotoxic side effects such as dose-dependent cardiac damage, morphologically defined necrosis and bleeding. Hypericum triquetrifolium Turra. (HT) shows anti-oxidative and anticarciogenic properties with its rich phenolic contents. The current study was designed to investigate the possible protective effect of HT on CYP-induced cardiotoxicity. Albino rats were randomly divided into 9 groups, each included 7 animals. Serum creatine kinase-MB (CK-MB), malondialdehyde (MDA), aspartate transaminase (AST), glutathione (GSH), total antioxidant (TAC) and total oxidant capacity (TOC) levels were investigated. Furthermore, the cardiac tissue samples were investigated histopatologically. While the levels of serum CK-MB, MDA, AST and TOC were high, the levels of serum GSH and TAC levels were low in the CYP groups. It was also observed that CYP-induced cardiotoxicity was dose dependent. In the treatment with CYP plus HT doses there was observed an essential decrease in the CYP cardiotoxicity; decreased cell damage and oxidative stress parameters and also increased GSH and TAC levels. Based on our findings, it can be proposed that HT seed methanol extract was a strong candidate in preventing the CYP-induced cardiotoxicity.

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“…Νεότερες μελέτες έδειξαν επίσης πως ο κρόκος προστατεύει από τις τοξικές επιδράσεις και άλλων αντινεοπλασματικών φαρμάκων όπως της κυκλοφωσφαμίδης και της μιτομυκίνης-C. Ειδικότερα η χορήγηση κρόκου σε πειραματόζωα ανέστειλε τις βλάβες που προκαλούν αυτοί οι αλκυλιωτικοί παράγοντες στο DNA κυττάρων του μυελού των οστών, ενώ σε πιο πρόσφατη μελέτη η χορήγηση κροκίνης σε επίμυες (10 mg/kg po για 6 ημέρες) ανταγωνίστηκε σημαντικά την νεφροτοξική και ηπατοτοξική δράση της κυκλοφωσφαμίδης, μέσω αντιοξειδωτικών μηχανισμών (Premkumar et al, 2006;Jnaneshwari et al, 2013).…”

Section: βιολογικές δράσειςunclassified

Διερεύνηση της δράσης των παραγώγων του Crocus sativus L. επί του κεντρικού νευρικού συστήματος στον επίμυ

Γεωργιάδου¹

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Crocus sativus L. is a rare plant, known since antiquity, which is cultivated in countries ofthe Mediterranean sea and of central Asia. The dried red stigmas of its flowers consist the drugand contain significant amounts of water-soluble carotenoids, known as crocins. Crocins arecrocetin glycosides and are considered responsible for the plant’s extensive therapeuticproperties.Various studies have demonstrated crocins’ chemopreventive, antitumoral, antioxidant,anti-inflammatory and cardioprotective properties. Regarding the central nervous system there isevidence that crocins act beneficially in learning and memory processes, exhibit analgesic effectsand alleviate symptoms in experimental models of epilepsy. Furthermore clinical studies haverevealed their antidepressant effect. Since it remains unknown if this drug affects otherpathophysiological routes of the central nervous system, the aim of the present study was toinvestigate the possible beneficial action of crocins on experimental models of anxiety,obsessive-compulsive disorder and schizophrenia.In order to examine the effect of crocins on anxiety we selected the light/dark test, anexperimental model which evaluates the anxiolytic action of compounds in rodents and is basedon their innate aversion to brightly illuminated areas. Results showed that crocins exhibit aremarkable anxiolytic effect, similar to that of diazepam.For the evaluation of crocins’ effects on obsessive-compulsive disorder we selectedm–chlorophenylpiperazine (m-CPP), a serotoninergic 5–ΗΣ2c agonist, which is known to induceexcessive self-grooming in rats. Excessive self- grooming is considered as a model ofobsessive-compulsive behavior in rodents. The analysis of the results demonstrated that crocinsantagonized the action of mCPP and reduced the time spent by rats in self-grooming.Finally in order to examine crocins’ efficacy in experimental models of schizophrenia weused ketamine, a non-competitive NMDA antagonist, which in subanesthetic dosage produces apsychotomimetic syndrome, characterized by hyperlocomomotion, ataxia, stereotypies, socialwithdrawal and working memory deficits. To determine crocins’ action against the whole spectrumof symptoms we performed three behavioral techniques: an open field test for the motordisorders, which are considered analogs of positive symptoms of schizophrenia, the socialinteraction test for the evaluation of social withdrawal, which serves as a model for the negativesymptoms and the novel object recognition task for the memory deficits, which mimic thecognitive deficits of patients with schizophrenia. Administration of crocins alleviated the motordisorders and antagonized the social withdrawal and memory deficits, caused by ketamine

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Crocin, a dietary colorant mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines

Abstract: The results obtained suggest the protective nature of crocin against CP-induced oxidative damage/inflammation and organ toxicity.

Cited by 70 publications

References 35 publications

Fertility preservation in cancer patients: attenuation of chemotherapy-induced ovarian damage by oral administration of phytochemical carotenoids in an animal model

Fertility preservation in cancer patients: attenuation of chemotherapy-induced ovarian damage by oral administration of phytochemical carotenoids in an animal model

Cardioprotective effects of Hypericum triquetrifolium Turra. against cyclophosphamide related cardiotoxicity in rats

Διερεύνηση της δράσης των παραγώγων του Crocus sativus L. επί του κεντρικού νευρικού συστήματος στον επίμυ

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