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Chlorpyrifos (CPF), considered one of the most potent organophosphates, causes a variety of human disorders including neurotoxicity. The current study was designed to evaluate the efficacy of hesperidin (HSP) in ameliorating CPF-induced neurotoxicity in rats. In the study, rats were treated with HSP (orally, 50 and 100 mg/kg) 30 min after giving CPF (orally, 6.75 mg/kg) for 28 consecutive days. Molecular, biochemical, and histological methods were used to investigate cholinergic enzymes, oxidative stress, inflammation, and apoptosis in the brain tissue. CPF intoxication resulted in inhibition of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) enzymes, reduced antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and elevation of malondialdehyde (MDA) levels and carbonic anhydrase (CA) activities. CPF increased histopathological changes and immunohistochemical expressions of 8-OHdG in brain tissue. CPF also increased levels of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-κB) while decreased levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Furthermore, CPF increased mRNA transcript levels of caspase-3, Bax, PARP-1, and VEGF, which are associated with apoptosis and endothelial damage in rat brain tissues. HSP treatment was found to protect brain tissue by reducing CPF-induced neurotoxicity. Overall, this study supports that HSP can be used to reduce CPF-induced neurotoxicity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Paclitaxel (PTX) is widely used to treat a number of malignancies, although it has toxic side effects. Hesperidin (HES) has a wide range of biological and pharmacological properties, including anti-inflammatory and antioxidant abilities. This research aims to investigate the role of HES in PTX-induced testicular toxicity. For 5 days, 2 mg/kg/bw i.p. of PTX was administered to induce testicular toxicity. Rats were administered oral dosages of 100 and 200 mg/kg/bw HES for 10 days after PTX injection. The mechanisms of inflammation, apoptosis, endoplasmic reticulum (ER) stress, and oxidants were investigated using biochemical, genetic, and histological techniques. As a result of PTX administration, decreased antioxidant enzyme (superoxide dismutase, catalase, and glutathione peroxidase) activities and increased malondialdehyde level were regulated, and the severity of oxidative stress was reduced. NF-κB, IL-1β and TNF-α levels, which are among the increased inflammation parameters caused by PTX, decreased with HES administration. Although AKT2 gene expression decreased in PTX administered rats, it was determined that HES administration up-regulated AKT2 mRNA expression. Anti-apoptotic Bcl-2 decreased with PTX administration, and apoptotic Bax and Caspase-3 increased while HES administration reverted these effects towards control level. As a result of toxicity, the increase in ATF6, PERK, IRE1α, GRP78 levels caused prolonged ER stress, and this activity was diminished with HES and tended to regress. While all data were evaluated, Paclitaxel caused damage by increasing inflammation, apoptosis, ER stress and oxidant levels in testicular tissue, and Hesperidin showed a protective effect by correcting the deterioration in these levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Paclitaxel (PTX) is a widely used chemotherapeutic drug particularly effective against lung, breast, and ovarian cancer, though its usefulness is limited due to its multi-organ toxicity. The mechanisms underlying PTX toxicity are currently not yet known and there are no approved treatments for its control or prevention. This study aimed to investigate whether hesperidin (HSP) had a protective effect on paclitaxel-induced hepatotoxicity and nephrotoxicity from biochemical, and molecular perspectives. The rats were administered PTX 2 mg/kg, b.w. intraperitoneally for the first 5 consecutive days, then 100 or 200 mg/kg b.w. HSP orally for 10 consecutive days. Our results demonstrated that HSP decreased the PTX induced lipid peroxidation, improved the serum hepatic and renal functions (by decreasing the levels of AST, ALT, ALP, urea, and creatinine), and restored the liver and kidney antioxidant armory (SOD, CAT, GPx, and GSH). HSP also significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-1β, IL-6, MAPK 14, Caspase-3, Bax, LC3A, LC3B, MMP2, and MMP9 whereas caused an increase in levels of Nrf2, HO-1, and Bcl-2 in the kidney and liver of PTX-induced rats. In addition, caspase-3, Bax, and Bcl-2 protein levels were examined by Western blot analysis, and it was determined that HSP decreased caspase-3 and Bax protein levels, but increased Bcl-2 protein levels. The findings of the study suggest that HSP has chemopreventive potential against PTX-induced hepatorenal toxicity plausibly through the attenuation of oxidative stress, inflammation, apoptosis, and autophagy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Excessive fluoride intake has been reported to cause toxicities to brain, thyroid, kidney, liver and testis tissues. Hesperidin (HSP) is an antioxidant that possesses anti-allergenic, anti-carcinogenic, anti-oxidant and anti-inflammatory activities. Presently, the studies focusing on the toxic effects of sodium fluoride (NaF) on heart tissue at biochemical and molecular level are limited. This study was designed to evaluate the ameliorative effects of HSP on toxicity of NaF on the heart of rats in vivo by observing the alterations in oxidative injury markers (MDA, SOD, CAT, GPX and GSH), pro-inflammatory markers (NF-κB, IL-1β, TNF-α), expressions of apoptotic genes (caspase-3, -6, -9, Bax, Bcl-2, p53, cytochrome c), levels of autophagic markers (Beclin 1, LC3A, LC3B), expression levels of PI3K/Akt/mTOR and cardiac markers. HSP treatment attenuated the NaF-induced heart tissue injury by increasing activities of SOD, CAT and GPx and levels of GSH, and suppressing lipid peroxidation. In addition, HSP reversed the changes in expression of apoptotic (caspase-3, -6, -9, Bax, Bcl-2, p53, cytochrome c), levels of autophagic and inflammatory parameters (Beclin 1, LC3A, LC3B, NF-κB, IL-1β, TNF-α), in the NaF-induced cardiotoxicity. HSP also modulated the gene expression levels of PI3K/Akt/mTOR signaling pathway and levels of cardiac markers (LDH, CK-MB). Overall, these findings reveal that HSP treatment can be used for the treatment of NaF-induced cardiotoxicity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Fluoride is an element with toxic properties and has been proven to have some adverse effects on many soft tissues, including brain tissue. This study aims to evaluate the protective effects of hesperidin on sodium fluoride (NaF)-induced neurotoxicity in rats by biochemical and molecular methods. The animals were randomly divided into five groups of seven rats each as Control, hesperidin, NaF (600 ppm), NaF + hesperidin (100 mg/kg, b.w.), and NaF + hesperidin (200 mg/kg, b.w.), respectively; orally for two weeks. Hesperidin reduced lipid peroxidation and increased activities of SOD, CAT and GPx and levels of GSH in NaF-induced brain tissue. Hesperidin also showed anti-inflammatory and anti-autophagic effects by decreasing levels of NF-κB, IL-1B, TNF-α, Beclin-1, LC3A, and LC3B in NaF-induced brain tissue. Moreover, hesperidin was able to down-regulate the mRNA transcript levels of apoptosis and endoplasmic reticulum stress markers such as caspase-3, Bax, Bcl-2, PERK, IRE1, ATF6, and GRP78 in NaF-induced neurotoxicity. Hesperidin also reduced the adverse effects caused by NaF by modulating the PI3K/Akt/mTOR signaling pathway. These results demonstrate that hesperidin exhibits neuroprotective effects against NaF-induced neurotoxicity in rats by ameliorating inflammation, apoptosis, autophagy, and endoplasmic reticulum stress., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this study, the potential effects of hesperidin (HES) on chronic toxicity caused by abamectin (ABM) in the testicular tissue were investigated through oxidative stress, inflammation, endoplasmic reticulum stress (ERS), apoptosis, and autophagy pathways. Male Sprague Dawley rats were used in the study. Animals in the ABM group were orally administered 1 mg/kg ABM every other day for 28 days, while HES used against ABM was given at 100 or 200 mg/kg 30 min after ABM administration for 28 days. Markers of oxidative stress, inflammation, ERS, apoptosis, and autophagy in the testicular tissues removed after the animals are sacrificed were analyzed using biochemical, real-time polymerase chain reaction (RT-PCR), or western blot techniques. The results obtained showed that ABM caused oxidative stress, and triggered ERS, inflammation, apoptosis, and autophagy. On the other hand, HES showed antioxidant effect by increasing superoxide dismutase, catalase, glutathione peroxidase enzyme activities, and glutathione levels in testis tissue and attenuated lipid peroxidation. Accordingly, MAPK14 reduced the NF-κB, IL-1β, TNF-α, and IL-6 expression levels, presenting an anti-inflammatory effect. In addition, Bax protected against apoptosis and autophagy by reducing the caspase-3, beclin-1, LC3A, and LC3B expressions, and increasing Bcl-2 expression. It was observed that HES also interrupted the JAK2/STAT3 signaling pathway by suppressing IL-6 expression. Taken into consideration together, HES provided significant protection against the destruction caused by ABM in testicular tissue with antioxidant, anti-inflammatory, antiapoptotic, and anti-autophagic effects. Thus, it was revealed that HES has the potential to serve as an alternative treatment option in ABM toxicity., (© 2021 Wiley Periodicals LLC.)

Paclitaxel (PTX), which is widely used in the treatment of solid tumors, leads to dose limitation because it causes peripheral neuropathy. This study was conducted to evaluate the potential effects of hesperidin (HES), which has various biological and pharmacological properties, against PTX-induced sciatic nerve damage. For this purpose, Sprague Dawley rats were given PTX 2 mg/kg/b.w for 5 days, then 100 or 200 mg/kg/b.w HES for 10 days, and behavioral tests were conducted at the end of the experiment. The data obtained show that PTX-induced MDA, NF-κB, IL-1β, TNF-α, COX-2, nNOS, JAK2, STAT3, and GFAP levels decreased with HES administration. Moreover, it was observed that SOD, CAT, and GPx activities inhibited by PTX increased with HES administration. It was determined that PTX caused apoptosis in the sciatic nerve by increasing Caspase-3 and Bax levels and suppressing Bcl-2 levels. HES, on the other hand, showed an anti-apoptotic effect, increasing Bcl-2 levels and decreasing Caspase-3 and Bax levels. Also, it was observed that PTX could cause endoplasmic reticulum stress (ERS) by increasing PERK, IRE1, ATF-6, GRP78 and CHOP mRNA transcript levels, while HES could alleviate ERS by suppressing them. The results indicate that neuropathic pain associated with PTX-induced peripheral neuropathy can be alleviated by HES administration and that it is a promising compound for cancer patients. In addition, it is thought that the results of the present study contain information that will shed light for researchers regarding further studies to be conducted with HES., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study aimed to investigate the effect of hesperidin on reproductive damage caused by diabetes mellitus. A total of 24 adult male rats were divided into four groups: control group, hesperidin group, diabetes mellitus group, and diabetes mellitus + hesperidin group. The study was conducted for 4 weeks. At the end of the study, the rats were sacrificed and testicular oxidative stress markers (MDA, GSH, GSH-Px, SOD, and CAT), DNA damage in testes (8-OHdG), and routine sperm parameters were evaluated. According to the results of the study, most of the parameters were similar in the control and hesperidin groups but CAT activity in the hesperidin group was statistically higher than the control group. Also, diabetes mellitus (DM) significantly increased MDA levels and decreased enzymatic antioxidant (GSH-Px, SOD, CAT) activities and nonenzymatic (GSH) antioxidant levels. On the other hand, hesperidin supplementation significantly decreased oxidative stress and increased enzymatic antioxidant activities and nonenzymatic antioxidant levels due to the antioxidant effect. Also, DM increased DNA damage levels in testicular tissue and hesperidin supplementation significantly decreased DNA damage levels in testes of diabetic male rats. Besides, sperm motility significantly decreased while abnormal sperm rate and dead sperm rate were significantly increased in diabetic rats. Hesperidin supplementation significantly reduced these side effects in diabetic rats. In conclusion, hesperidin supplementation could be beneficial for decreasing the side effects on the male reproductive system caused by DM in rats. PRACTICAL APPLICATIONS: Diabetes is an important metabolic disease, affecting quality of life and fertility. Hesperidin has an antioxidant effect and has a potential protective effect on reproductive toxicity in diabetic male rats. Hesperidin decreased oxidative stress, and DNA damage in testis resulted from hyperglycemia and improved sperm quality in diabetic rats. The hesperidin supplementation could be a good strategy to protect male fertility in diabetic patients., (© 2021 Wiley Periodicals LLC.)

Aim: High dose of fluoride intake is associated with toxic effects on liver and kidney tissues. One approach to tackle these toxicities is using natural antioxidants as supplements. This study evaluated the ameliorative effects of hesperidin (HSP) against sodium fluoride (NaF)-induced hepatotoxicity and nephrotoxicity in wistar albino rats., Materials and Methods: In the present study, the rats were randomly allocated into five groups of seven male rats each group: control, NaF (600 ppm), HSP-200, NaF + HSP-100 and NaF + HSP 200., Key Findings: Hepatic and renal injuries induced by NaF were confirmed by the alteration in kidney function parameters in the serum (urea and creatinine), levels of liver enzymes (ALT, ALP and AST), activities of the antioxidant enzymes (SOD, CAT and GPx) and levels of inflammatory markers (NF-κB, IL-1β and TNF-α). NaF also inhibited PI3K/Akt/mTOR pathway, increased levels of autophagic markers (Beclin-1, LC3A and LC3B) and expression levels of apoptotic and anti-apoptotic proteins (Bax, Bcl-2, cytochrome c, p53 and procaspase-3) in the liver and kidney tissues. Administration of HSP concurrently with NaF significantly ameliorated the deviation in the above-studied parameters., Significance: The results of the current study revealed that HSP could be used as a beneficial adjuvant that confers protection against NaF-induced liver and kidney damage through antioxidant, anti-inflammatory, anti-apoptotic and anti-autophagic mechanisms., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this study, we investigated the effects of hesperidin (HSP) on oxidants/antioxidants status, inflammation, apoptotic, and autophagic activity in hepato-renal toxicity induced by chronic chlorpyrifos (CPF) exposure in rats. We used a total of 35 male albino rats in five groups of seven: control, HSP 100, CPF, CPF + HSP50, and CPF + HSP100. After rats were sacrificed, blood, liver, and kidney samples were collected. Serum levels of aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP), creatinine, and urea were tested. Then, contents of the superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GPx), and glutathione (GSH) were measured to detect the level of oxidative stress in rat liver and renal tissues. We measured inflammatory and autophagy markers of chlorpyrifos induced oxidative stress in the liver and kidney tissues including TNF-α, iNOS, IL-1 β, COX-2, NF-κB, MAPK14, and Beclin-1 using ELISA. Histopathological findings were also examined followed by immunohistochemical determination of 8-OHdG expression. Real-time PCR (RT-PCR) was used to examine Cas-3, Bax, Bcl-2, PARP-1, and VEGF, which are associated with apoptosis, autophagy, DNA, and endothelial damage, respectively. In addition, PARP-1 activity was supported by western blot and immunofluorescence, VEGF activity was supported by western blot methods. Treatment with HSP reduced the effect of CPF on ALT, AST, ALP, and total proteins, and increased its effect on tissue antioxidants. PARP/VEGF, apoptotic, pro-apoptotic, anti-apoptotic, and autophagic gene expressions were regulated, and Caspase-3 and Bax expressions were decreased; Bcl-2 expression increased in both the liver and kidney samples, and positivity of 8-OHdG and PARP-1 were reduced in the CPF plus HSP-treated group. Overall, the study demonstrates that HSP may reduce the effects of hepato-renal toxicity caused by CPF by regulating oxidative stress, inflammation, apoptosis, autophagy, and PARP/VEGF genes at biochemical, cellular, and molecular levels., (© 2021 Wiley Periodicals LLC.)

In the scope of the study, the protective effect of hesperidin (HES), a flavanone glycoside, was investigated against sodium arsenite (NaAsO 2 , SA) induced heart and brain toxicity. For this purpose, 35 Sprague-Dawley male rats were divided into 5 different groups, 7 in each group. Physiological saline was given to the first group. Dose of 200 mg/kg of HES to the second group, 10 mg/kg dose of SA to the 3rd group, 100 mg/kg HES and 10 mg/kg SA to the 4th group, 200 mg/kg HES, and 10 mg/kg SA to the 5th group were given orally for 15 days. At the end of the study, biochemical, histopathological, and immunohistochemical examinations were performed on the heart and brain tissues of the rats. According to the results, SA increased malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and decreased glutathione (reduced, GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in both tissues. Also, it increased cardiac lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CK-MB) activities and cardiac troponin-I level (cTn-I), cerebral acetylcholine esterase activity, nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), and cysteine aspartate-specific protease-3 (caspase-3) levels. In addition, as a result of histopathological examination, it was determined that SA damaged tissue architecture, and as a result of immunohistochemical examination, it increased cardiac Bcl-2-associated X protein (Bax) and cerebral glial fibrillary acidic protein (GFAP) expression. The results have also shown that HES co-treatment has an antioxidant, anti-inflammatory, antiapoptotic effect on SA-induced toxicity and aids to protect tissue architecture by showing a regulatory effect on all values. Consequently, it was determined that HES co-treatment had a protective effect on SA-induced heart and brain toxicity in rats.

This study has been conducted to investigate the effect of hesperidin on colistin-induced reproductive damage in male rats. Twenty-four adult male Sprague Dawley rats were used as animal material. They were divided into four groups: control group, received physiological saline for 7 days by oral gavage; hesperidin group, received 300 mg/kg day hesperidin for 7 days; colistin group, received 73 mg/kg (total dose) colistin during 7 days; and colistin + hesperidin group, received 300 mg/kg day hesperidin following the colistin treatment. At the end of the study, routine spermatological parameters and biochemical evaluations were assayed. Also, apoptosis and autophagy biomarkers in testes were evaluated. Colistin increased oxidative stress, apoptosis and autophagy expression levels in testis. Hesperidin supplementation significantly decreased the oxidative stress levels in the testes of the colistin + hesperidin group when compared to the colistin group. The highest apoptosis and autophagy expression levels were detected in the colistin group. These values were statistically lower in the colistin + hesperidin group when compared to the colistin group. Colistin treatment decreased the percentage of sperm motility and increased sperm abnormality. Hesperidin supplementation mitigated significantly mentioned side effects compared to the colistin group. In conclusion, hesperidin supplementation can be a good strategy to mitigate colistin-induced testicular toxicity., (© 2020 Wiley-VCH GmbH.)

The present study was conducted to investigate the protective effects of hesperidin (HSP) against sodium arsenite (SA)-induced nephrotoxicity and hepatotoxicity in rats. Thirty-five male Sprague Dawley rats were divided into five groups as follows: control, HSP, SA, SA + HSP 100, and SA + HSP 200. Rats were orally gavaged with SA (10 mg/kg body weight) and HSP (100 and 200 mg/kg body weight) for 15 days. SA increased oxidative damage by decreasing antioxidant enzyme activities, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and glutathione (GSH) level and increasing malondialdehyde (MDA) level in the kidney and liver tissues. In addition, it increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and serum urea and creatinine levels. Furthermore, SA caused inflammation, apoptosis, and oxidative DNA damage by increasing tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), cysteine aspartate-specific protease-3 (caspase-3), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the kidney and liver tissues and by increasing liver p53 and kidney interleukin-6 (IL-6) expressions. In other words, HSP administration reduced apoptosis, oxidative stress, inflammation, and oxidative DNA damage significantly in SA-induced kidney and liver tissues depending on dose. In this study, it was seen that HSP showed a protective effect against SA-induced kidney and liver toxicity.

Purpose: Allergic rhinitis is an immunoglobulin-E (Ig-E)-mediated response driven by type 2 helper T cells. Hesperidin and thymol are biological agents that possess antioxidant and anti-inflammatory characteristics. The purpose of this study was to investigate the effects of hesperidin and thymol in rats with ovalbumin-induced allergic rhinitis., Methods: Thirty adult Sprague-Dawley rats were randomly assigned into five groups, each containing six animals. The first group constituted the negative control group, while the remaining groups were exposed to an ovalbumin-induced model of allergic rhinitis. In the provocation stage, 4 mL/kg saline was administered to the positive control group, 10 mg/kg desloratadine to the reference group, 100 mg/kg hesperidin to the hesperidin group, and 20 mg/kg thymol to the thymol group, all by gastric lavage for 7 days. Nasal symptoms were scored on day 22. Rats were then sacrificed, and intracardiac blood specimens were collected to measure plasma total Ig-E, IL-5, IL-13, total antioxidant capacity (TAC), and total oxidant status (TOS) levels. Nasal tissues were extracted for histopathological and immunochemical examination., Results: Nasal symptom scores were highest in the positive control group, while hesperidin and thymol ameliorated these symptoms to the same extent as desloratadine. Ig-E, IL-5, IL-13, and TOS levels increased, while TAC levels decreased significantly in the allergic rhinitis group compared to the other groups. Significant improvement in these parameters was observed in both the hesperidin and thymol groups. At histopathological and immunohistochemical examination of the nasal cavity, severe allergic inflammation and severe TNF-α expression was determined in rats from the allergic rhinitis group. Mild inflammatory changes and mild TNF-α expression were observed in all three treatment groups., Conclusion: Both hesperidin and thymol were effective in suppressing allergic symptoms and inflammation in the treatment of allergic rhinitis.

In our work, it was purposed to investigate the effects of sodium arsenite (SA) and hesperidin (HSP) administered to rats on some metabolic enzymes including carbonic anhydrase (CA), aldose reductase (AR), paraoxonase-1 (PON1), α-glycosidase (α-Gly), butyrylcholine esterase (BChE), acetylcholine esterase (AChE) enzymes activities in the brain, heart, liver, testis, and kidney tissues of rats. CA activities were significantly decreased in testis, liver, and heart tissues of rats given HSP, SA, SA+HSP-100, and SA+HSP-200 compared to control (p < 0.05). In liver tissue, AChE and BChE enzymes activities were significantly reduced given in all groups. In all tissues, α-Gly activity was reduced given in all groups. In the current study, aldose reductase enzyme activity was reduced significantly in testis, brain, and heart tissues of all groups compared to standard (p < 0.05). PON1 enzyme activity was increased significantly in kidney and liver tissues of rats HSP groups and decreased SA groups compared to control. PRACTICAL APPLICATIONS: α-Glycosidase is the key enzyme involved in the digestion of the carbohydrate. Another enzyme α-amylase hydrolyzes the α-linked polysaccharide derivatives into oligosaccharide molecules, and α-glycosidase enzymes, which are characterized in small intestine, catalyze the final stage in the digestive mechanism of carbohydrate molecule to release absorbable monosaccharides like glucose. Conforming to the cholinergic hypothesis, impairment of the cholinergic pathways plays a good role in the development of neurodegenerative diseases like depression, schizophrenia, Alzheimer's disease (AD) problems with the regulation of traumatic brain injury and sleep. The AD is the main reason for dementia disease, and mild to moderate cases are generally treated with AChE inhibitors. Human CA inhibitor compounds are clinically used for more than 70 years as antiglaucoma and diuretics drugs., (© 2018 Wiley Periodicals, Inc.)

This study aimed to investigate whether hesperidin and chrysin antioxidants have protective effects on renal injury induced by colistin in rats. Renal lipid peroxidation, total glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) enzyme activities, serum urea and creatinine levels, as well as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were determined. Injuries to the proximal and distal tubules were determined using histopathological and double immunohistochemistry examinations. The results showed that hesperidin and chrysin significantly decreased the levels of MDA and inflammatory parameters and significantly increased GSH, SOD, CAT, and GSH-Px levels against colistin-induced renal injury. The results also showed that cystatin C and calbindin D28K immunopositivities significantly increased through hesperidin and chrysin treatment. Hesperidin and chrysin alleviated the renal injury induced by colistin via anti-oxidant and anti-inflammatory activities. Thus, hesperidin and chrysin could attenuate colistin-induced nephrotoxicity via antioxidant and anti-inflammatory activities. Addition of hesperidin or chrysin to the treatment protocol of colistin treatment might benefit patient treatment in terms of the prevention of colistin-induced renal injury., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)