The Microalga Skeletonema marinoi Induces Apoptosis and DNA Damage in K562 Cell Line by Modulating NADPH Oxidase.

Chronic myeloid leukemia (CML) is a myeloproliferative disease that activates multiple signaling pathways, causing cells to produce higher levels of reactive oxygen species (ROS). Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are a major generator of ROS in leukemia, and marine natural products have shown promising activities for the treatment of hematopoietic malignancies. In the present study, we investigated the effect of the marine microalga Skeletonema marinoi (S.M.), a ubiquitous diatom that forms massive blooms in the oceans, on the human leukemia cell line K562. The effects of S.M. extract on cell viability, production of ROS, nitric oxide (NO), and apoptosis were examined. In this preliminary work, S.M. was able to decrease cell viability (p < 0.05) and increase apoptosis levels (p < 0.05) in K562 cells after 48 h of treatment. In addition, the levels of NOX, NO, and malondialdehyde (MDA) were reduced in K562-treated cells (p < 0.05), whereas the levels of SOD, CAT, and GPx increased during treatment (p < 0.05). Finally, analyzing Bax and Bcl-2 expression, we found a significant increase in the proapoptotic protein Bax and a sustained decrease in the antiapoptotic protein Bcl-2 (p < 0.05) in the K562-treated cells.

Red orange and lemon extract prevents the renal toxicity induced by ochratoxin A in rats.

In this work, we investigated the effects of red orange and lemon extract (RLE) on ochratoxin A (OTA)-induced nephrotoxicity. In particular, we analyzed the change in renal function and oxidative stress in Sprague-Dawley rats treated with OTA (0.5 mg/kg body weight, b.w.) and with RLE (90 mg/kg b.w.) by oral administration. After OTA treatment, we found alterations of biochemical and oxidative stress parameters in the kidney, related to a severe decrease of glomerular filtration rate. The RLE treatment normalized the activity of antioxidant enzymes and prevented the glomerular hyperfiltration. Histopathological examinations revealed glomerular damages and kidney cortex fibrosis in OTA-rats, while we observed less severe fibrosis in OTA plus RLE group. Then, we demonstrated that oxidative stress could be the cause of OTA renal injury and that RLE reduces this effect.

Effects of δ-tocotrienol on ochratoxin A-induced nephrotoxicity in rats.

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

Effects of antioxidants on apoptosis induced by dasatinib and nilotinib in K562 cells.

In clinical practice for the treatment of chronic myeloid leukemia, second generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL and Src family kinase were developed to clinically overcome imatinib resistance. In this study, we wanted to test the ability of some antioxidants such Resveratrol (RES) or a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) or δ-tocotrienol (δ-TOCO) to interact with DAS and NIL on viability, reactive oxygen species (ROS) production, lipid peroxidation, and apoptosis. To test the possible mechanisms of action of such antioxidants, we utilized N-acetyl-L-cysteine (NAC) a specific inhibitor ROS production or PP1 a specific Src tyrosine kinase inhibitor or BAPTA a specific chelator of intracellular calcium. Our data demonstrated: 1) RES, rMnSOD, δ-TOCO, and NAC, at dose used, significantly reduced the intracellular levels of MDA induced by DAS or NIL; 2) RES, rMnSOD, and δ-TOCO increased the intracellular ROS levels; 3) The increase ROS levels is related to higher levels of oligonucleosomesi induced by DAS and NIL and that NAC significantly reduced this activity. Interestingly, our data showed that apoptotic activity of DAS and NIL have significantly increased the production of oligonucleosomes by triggering excessive ROS generation as well as functionality of SERCA receptors.

Effect of rMnSOD on Sodium Reabsorption in Renal Proximal Tubule in Ochratoxin A-Treated Rats.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that represent toxic real threat for human beings and animal health. In this study we evaluated the effect of a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) on oxidative stress and on the alterations of fluid reabsorption in renal proximal tubule (PT) as possible causes of OTA nephrotoxicity. Finally, we have measured the concentration of O2- in the kidney through dihydroethidium assay (DHE) and nitric oxide (NO) concentration through nitrites and nitrates assay. Male Sprague Dawley rats weighing 120-150 g were treated for 14 days by gavage, as follows: Control group, 12 rats received a corresponding amount of saline solution (including 10% DMSO); rMnSOD group, 12 rats treated with rMnSOD (10 µg/kg bw); OTA group, 12 rats treated with OTA (0.5 mg/kg bw) dissolved in 10% DMSO and then scaled to required volume with corn oil; rMnSOD + OTA, 12 rats treated with rMnSOD (10 µg/kg bw) plus OTA (0.5 mg/kg bw). Our results have shown that rMnSOD restores the alteration of reabsorption in PT in rats treated with OTA plus rMnSOD, probably through the response to pressure natriuresis, where nitric oxide plays a key role. Moreover, rMnSOD prevents the nephrotoxicity induced by OTA probably restoring the balance between superoxide and NO that is most probably the cause of hypertension and renal functional alterations through the inhibition of NO synthase. In conclusion these data provide important information for understanding of mechanism of toxic action of OTA. J. Cell. Biochem. 119: 424-430, 2018. © 2017 Wiley Periodicals, Inc.

Toxicity of Crepis lacera in grazing ruminants.

BACKGROUND: Crepis lacera is a plant from the Asteraceae family that is common in the Mediterranean region. Farmers believe that this plant may be deadly to small ruminants in areas of southern Italy. However, scientific evidence is lacking, and no proof exists that C. lacera is toxic to ruminants. Necropsies conducted on four sheep revealed lesions in their livers and kidneys. RESULTS: In the current study, we described sheep poisoning and isolated secondary metabolites from Crepis lacera to assess the metabolites' biological activity both in vitro and in vivo. Phytochemical study of the aerial portions of Crepis lacera led to the isolation of five sesquiterpene lactones and two phenolic compounds. Cellular viability was evaluated in cell cultures of the bovine kidney cell line Madin Darby Bovine Kidney (MDBK) after incubation with phytochemicals. Our results showed that three sesquiterpene lactones, 8-epidesacylcynaropicrin-3-O-ß-glucopyranoside (2), 8-epigrosheimin (3), and 8-ß-hydroxydehydrozaluzanin C (4), were cytotoxic after 48 h of incubation. In addition, in the in vivo study, animals that received 1 mg/kg body weight (bw) of Crepis lacera extract and were then sacrificed after 48 h showed significant lesions in their liver, lungs and kidneys. These lesions were also found in rats that received 2 mg/kg bw of the same extract and sacrificed after 24 and 48 h. CONCLUSIONS: These results validate the hypothesis that C. lacera is potentially dangerous when ingested in large quantities by grazing small domestic ruminants. Further studies are necessary to clarify the molecular mechanisms of Crepis spp. toxicity in animals.

The Palatal Window for Treating an Incompletely Augmented Maxillary Sinus.

Maxillary sinus augmentation through a lateral window is reported as one of the most predictable bone augmentation procedures before implant placement. The elevation of the membrane represents a delicate and crucial step that allows the creation of the space for the bone graft material. If the elevation is not completed, the regenerated bone might be inadequate for the implant placement. In this case, a new intervention will be necessary to complete the bone augmentation. Reaccessing from a lateral window, however, would be challenging due to thickness of the buccal boney wall because of the first grafting procedure; therefore, a different approach has to be used. The aim of this case report is to present the palatal window technique for treating incompletely augmented maxillary sinus. The detailed step-by-step diagnostic and surgical procedures are described, and the advantages and limitations of the technique are discussed through a review of the literature.

Comparison of Dasatinib, Nilotinib, and Imatinib in the Treatment of Chronic Myeloid Leukemia.

To overcome the drug resistance phenomenon induced by Imatibib (IM), in clinical practice, are often used second generation of tyrosine kinase inhibitors as Nilotinib (NIL); a such potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS), a inhibitor of BCR/ABL kinase, and inhibitor SrC family kinase. In this study we evaluated the in vivo effect of DAS, NIL, and IM on intracellular calcium concentration, oxidative stress, and apoptosis in peripheral blood leukocytes of 45 newly diagnosed patients with chronic myeloid leukaemia (CML-PBM). Our data demonstrated that treatment with DAS and NIL showed an higher modulating potential than IM on intracellular calcium concentration by inhibiting the thapsigargin, a sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor, and Lithium (Li) an inositol 1,4,5-triphosphate (InsP3) receptor inhibitor activities. Moreover our data demonstrated that NIL and DAS have significantly increased apoptosis more than IM by involving both intracellular calcium signaling as well as oxidative stress. The acquisition of the oxidative stress and calcium channels receptors values data could help the hematologist to modulate and improve the treatment of chronic myeloid leukaemia (CML) pathology.

Recombinant Mitochondrial Manganese Containing Superoxide Dismutase Protects Against Ochratoxin A-Induced Nephrotoxicity.

Ochratoxin A (OTA) is a natural mycotoxin, involved in the development of important human and animal diseases. In this work we have studied the role of oxidative stress in the development of OTA nephrotoxicity and the effect of a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) to prevent kidney damage induced by OTA. Blood pressure, glomerular filtration rate and renal histology were analyzed in control rats and in OTA treated rats. In addition, lipid peroxidation, catalase and superoxide dismutase productions were measured. Our data showed that animals treated with OTA presented hypertension and reduction of glomerular filtration rate (GFR). These effects are most probably related to an increase in the reactive oxygen species (ROS) productions. In fact, we have shown that treatment with rMnSOD restored the levels of blood pressure and GFR simultaneously. Moreover, we have noted that OTA induced alteration on glomerular and tubular degeneration and interstitial infiltrates and that use of rMnSOD combined with OTA prevent this renal histological damage confirming the potential therapeutic role in the treatment of rMnSOD OTA nephrotoxicity.

Prevention of nephrotoxicity induced by cyclosporine-A: role of antioxidants.

Cyclosporine A (CsA) is a powerful immunosuppressive drug used to prevent allograft rejection after organ transplantation as well as in human and veterinary medicine. Unfortunately, its use is hampered by its nephrotoxic effects. The mechanisms of CsA-induced hypertension and nephrotoxicity are not clear, but several studies suggest the possible involvement of free radicals. In this review we have summarized the effect of some antioxidants that we have used in the recent years, in combination with CsA, to better understand the exact mechanism of action of CsA and to try to open new perspectives in the treatment of CsA nephrotoxicity.

The Protective Effect of Apocynin on Cyclosporine A-Induced Hypertension and Nephrotoxicity in Rats.

Cyclosporine A (CsA) is the prototype of immunosuppressant drugs that has provided new perspectives in human and veterinary medicine to prevent organ transplant rejection and to treat certain autoimmune diseases and dermatologic diseases. Unfortunately, the treatment with CSA is often limited by severe adverse effects such as hypertension and nephrotoxicity. Some data suggest that reactive oxygen species (ROS) and the oxidative stress play an important role in its pathogenesis, in particular the superoxide (O2 (-)) that is the most powerful free radical generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase present mainly in the kidney. The present study has been designed to investigate the role of Apocynin a selective inhibitor of NADPH oxidase activity on cyclosporine-induced adverse effect. In this study, we have evaluated the effect of CsA, used alone or in association with Apocynin on blood pressure (BP), on glomerular filtration rate (GFR), on absoluted fluid reabsorption (Jv) in proximal tubule (PT), on O2 (-) concentration, and on nitric oxide (NO) production. We have demonstrated that CsA administration increases superoxide concentration in the aorta, decreases the NO concentration, reduces GFR and the Jv in PT, and induces a significant increase in BP. Moreover, we have shown that Apocynin treatment restores these hemodynamic alterations, as well as NO and superoxide productions. In conclusion, the reported data indicate that CsA induced nephrotoxicity and hypertension are related to NADPH oxidase activity, in fact Apocynin protects the kidney function and BP from toxic effects induced by CsA through the inhibition of NADPH oxidase activity.

Protective Effects of a Red Orange and Lemon Extract (RLE) on the Hepatotoxicity Induced by Ochratoxin A in Rats.

Ochratoxin A (OTA) is a highly potent mycotoxin that contaminates many kinds of food and feed sources. Its significant impact on human health and animal productivity makes it a topic of particular concern. The role of specific bioactive compounds used as dietary antioxidants is believed to be substantial due to their capacity to act as free radical scavengers. Because of the well-known oxidative stress induced by OTA, the primary objective of this work was to evaluate the antioxidant effects of a standardized powder extract recovered from citrus processing waste, red orange and lemon extract (RLE), on liver damage induced by OTA in a rat model. This study aimed to examine the impact of oral administration of RLE (90 mg/kg b.w.) on hepatic function and oxidative balance in Sprague-Dawley rats (n = 6/group) treated with OTA (0.5 mg/kg b.w.) over a period of 14 days. The administration of OTA alone resulted in both biochemical changes and an imbalance in redox status in the liver. However, the use of RLE alleviated the activity of antioxidant enzymes and dramatically decreased the serum levels of ALT (alanine aminotransferase), AST (aspartate aminotransferase), and ALP (alkaline phosphatase), providing evidence of its protective benefits. Based on the findings from liver histology tests, the administration of RLE resulted in mitigation of lymphoplasmacytic inflammation, steatosis, and necrosis in the OTA group. These results indicate that the novel phytoextract RLE holds potential for application in the field of nutraceuticals.

Red Orange and Lemon Extract Ameliorates the Renal Oxidative Stress and Inflammation Induced by Ochratoxin A through the Modulation of Nrf2.

BACKGROUND: The presence of ochratoxin A (OTA) in food and feed is a public health concern. OTA intoxication is caused by several mechanisms, one of which consists of the alteration of the antioxidant activity of the cell due to the oxidative stress (OS). In this context, the use of natural antioxidant substances could be a potential biological decontamination method of mitigating the negative outcomes induced by OTA. METHODS: we aimed to investigate how a red orange and lemon extract (RLE), rich in anthocyanins, would affect OTA-treated rats. The current work sought to clarify the renal protective efficacy of RLE in an OTA-treated rat model (RLE (90 mg/kg b.w.); OTA (0.5 mg/kg b.w.)) by investigating, thorough Western blot analysis, the involvement of the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. The OS parameters and inflammatory status were evaluated by spectrophotometry. The inflammatory infiltrates in the kidney were evaluated by immunohistochemical assays. RESULTS AND CONCLUSION: Our findings showed a significant increase in oxidative and inflammatory parameters after OTA exposure, while the OTA + RLE co-treatment counteracted both the inflammatory and OS damage through the modulation of the Nrf2 pathway.

A new recombinant MnSOD prevents the cyclosporine A-induced renal impairment.

BACKGROUND: Cyclosporine A (CsA) is one of the most frequently used anticalcineurinic drugs for preventing graft rejection and autoimmune disease. Its use is hampered by nephrotoxic effects, namely an impairment of the glomerular filtration rate (GFR) and hypertension. Evidence suggests that reactive oxygen species (ROS) play a causal role in the nephrotoxicity. The present study aims to investigate in vivo the effects of a new recombinant mitochondrial manganese-containing superoxide dismutase (rMnSOD), a strong antioxidant, on the CsA-induced nephotoxicity. METHODS: Rats were treated with CsA (25 mg/kg/day) alone or in combination with rMnSOD (10 µg/kg/day) for 7 days. At the end of the treatment, GFR was estimated by inulin clearance (mL/min/100 g b.w.) and the mean arterial pressure (MAP) was recorded through a catheter inserted in the carotid artery. Superoxide concentration within the cells of the abdominal aorta was quantified from the oxidation of dihydroethidium (DHE). In kidney tissues, ROS levels were measured by the 2'7' dichloroflurescin diacetate assay. Renal morphology was examined at the histochemistry level. RESULTS: CsA-treated rats showed a severe decrease in GFR (0.34 ± 0.17 versus 0.94 ± 0.10 in control, P < 0.001) which was prevented by rMnSOD co-administration (0.77 ± 0.10). CsA-injected animals presented with higher blood pressure which was unaffected by rMnSOD. ROS levels both in the aorta and in renal tissue were significantly increased by CsA treatment, and normalized by the co-administration with rMnSOD. This effect was, partly, paralleled by the recovery from CsA-induced morphological lesions. CONCLUSIONS: Administration of rMnSOD prevents CsA-mediated impairment of the GFR along with morphological alteration. This effect could be related to the inhibition of ROS.

Oxidative Status and Histological Evaluation of Wild Boars' Tissues Positive for Zearalenone Contamination in the Campania Region, Southern Italy.

Zearalenone (ZEN) is a mycotoxin produced by fungi belonging to the genera Fusarium spp. and commonly found in feed and food. It is frequently related to reproductive disorders in farm animals and, occasionally, to hyperestrogenic syndromes in humans. Nowadays, knowledge about ZEN effects on wild boars (Sus scrofa) is extremely scarce, despite the fact that they represent one of the most hunted game species in Italy. The aim of this study was to investigate how ZEN affects the liver, kidney, and muscle oxidative status and morphology of wild boars hunted in various locations throughout the province of Avellino, Campania Region, Southern Italy, during the 2021-2022 hunting season. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, as well as the malondialdehyde (MDA) levels, were assessed by colorimetric assays; tissue morphology was evaluated by hematoxylin-eosin and Masson's stains. Our data showed that ZEN contamination might result in oxidative stress (OS) and some histopathological alterations in wild boars' livers and kidneys rather than in muscles, emphasizing the importance of developing a wildlife monitoring and management strategy for dealing not only with the problem of ZEN but the surveillance of mycotoxins in general.

Zearalenone (ZEN) and Its Metabolite Levels in Tissues of Wild Boar (Sus scrofa) from Southern Italy: A Pilot Study.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by the fungi of the Fusarium genera, and is a contaminant of cereals and plant products. ZEN and its metabolites are considered endocrine disruptors, and could have various toxic effects on animals and humans. In recent years, there has been a significant demographic increase in wild boar (Sus scrofa) in many mountainous and hilly areas of Italy, including the Campania region, mainly due to global climate change. The wild boar can be defined as a generalist and omnivorous species capable of varying its diet; therefore, it can play a role as an environmental bioindicator towards contaminants such as mycotoxins. This study was conducted to evaluate, for the first time, the concentrations of ZEN and its metabolites in the liver, kidney, and muscle of 82 wild boars shot in their habitat by hunters with hunting permits in different localities of Avellino province (Campania region, Southern Italy) from 2021 to 2022. The samples were collected and analyzed with an SPE clean-up and high-pressure liquid chromatography method with fluorescence detection. The results indicated that ZEN and α-Zearalenol were present in most of the samples, suggesting that a plan to monitor these mycoestrogens is essential to achieve the goals of "One Health".

Imatinib treatment inhibit IL-6, IL-8, NF-KB and AP-1 production and modulate intracellular calcium in CML patients.

Imatinib (IM) is considered the gold standard for chronic myeloid leukemia (CML) treatment, although resistance is emerging as a significant problem. The proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) play an important role in cell proliferation, survival, and resistance to glucocorticoid-mediated cell death. Several transcription factors such as NF-KB and AP-1 are activated in response to physiopathological increases and modulation of intracellular calcium levels. Our previous study demonstrated that lymphocytes from CML patients showed dysregulated calcium homeostasis and oxidative stress. Alteration in ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation. In this study, we hypothesized that IL-6, IL-8, NF-kB, AP-1, and intracellular calcium may be used as selective and prognostic factors to address the follow-up in CML patients treated with imatinib. Our results demonstrated a significant down-regulation in IL-6 and IL-8 release as well as NF-kB and AP-1 activation in lymphomonocytes from Imatinib-treated patients, compared to samples from untreated patients. In parallel, IM treatment, in vivo and in vitro, were able to modulate the intracellular calcium concentration of peripheral blood mononuclear cells of CML patients by acting at the level of InsP(3) receptor in the endoplasmic reticulum and at the level of the purinergic receptors on plasma membrane. The results of this study show that measurements of NF-kB, AP-1, IL-6, IL-8, and intracellular calcium in CML patients treated with Imatinib may give important information to the hematologist on diagnostic criteria and are highly predictive in patients with newly diagnosed CML.

Hydrocortisone attenuates cyclosporin A-induced nephrotoxicity in rats.

Cyclosporin A (CsA) is the prototype of immunosuppressant drugs that have revolutionized the management of all transplantation and autoimmune diseases. Side effects of CsA mainly affecting the kidney but also observed in liver and heart, limit the therapeutic use of this drug after organ transplantation. The renal toxicity of CsA is attributed to reduced renal blood flow which leads to hypoxia-reoxygenation injury accompanied by excessive generation of oxygen-derived free radicals. In several therapeutic protocols, CsA is used in association with corticosteroids to obtain better therapeutic results. Recently, our studies showed that hydrocortisone (HY) has a protective effect on CsA-induced cardiotoxicity. In fact our previous results demonstrated that in rat cardiomyocytes, CsA toxicity is due to a calcium overload, which in turn induce lipid peroxidation and determines oxidative stress-induced cell injury. Treatment with HY effectively inhibits CsA-induced toxicity, decreasing lipid peroxidation as well as calcium intracellular concentration. In this study we evaluated in vivo the effects of CsA, used alone or in association with HY, on some parameters of renal dysfunction (blood urea nitrogen; BUN, creatinine, and cholesterol), malondialdheyde (MDA) levels, antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and apoptosis. CsA administration for 24 days resulted in a marked renal oxidative stress, which significantly deranged the renal functions. Treatment with CsA in association with HY significantly improved the renal dysfunction and renal oxidative status. This study clearly suggests the role of oxidative stress in the pathogenesis of CsA-induced nephrotoxicity.

Design, synthesis, biophysical and biological studies of trisubstituted naphthalimides as G-quadruplex ligands.

A series of trisubstituted naphthalimides have been synthesized and evaluated as telomeric G-quadruplex ligands by biophysical methods. Affinity for telomeric G-quadruplex AGGG(TTAGGG)(3) binding was first screened by fluorescence titrations. Subsequently, the interaction of the telomeric G-quadruplex with compounds showing the best affinity has been studied by isothermal titration calorimetry and UV-melting experiments. The two best compounds of the series tightly bind the telomeric quadruplex with a 2:1 drug/DNA stoichiometry. These derivatives have been further evaluated for their ability to inhibit telomerase by a TRAP assay and their pharmacological properties by treating melanoma (M14) and human lung cancer (A549) cell lines with increasing drug concentrations. A dose-dependent inhibition of cell proliferation was observed for all cellular lines during short-term treatment.

Curcumin Modulates Nitrosative Stress, Inflammation, and DNA Damage and Protects against Ochratoxin A-Induced Hepatotoxicity and Nephrotoxicity in Rats.

Ochratoxin A (OTA) is a fungal toxin of critical concern for food safety both for human health and several animal species, also representing a cancer threat to humans. Curcumin (CURC) is a natural polyphenol that has anti-apoptotic, anti-inflammatory, and antioxidant effects. The aim of this study was to investigate the cytoprotective effect of CURC against OTA-induced nephrotoxicity and hepatotoxicity through the study of the nitrosative stress, pro-inflammatory cytokines, and deoxyribonucleic acid (DNA) damage. Sprague Dawley rats were daily treated with CURC (100 mg/kg b.w.), OTA (0.5 mg/kg b.w), or CURC with OTA by oral gavage for 14 days. Our results demonstrated that OTA exposure was associated with significant increase of pro-inflammatory and DNA oxidative-damage biomarkers. Moreover, OTA induced the inducible nitric oxide synthase, (iNOS) resulting in increased nitric oxide (NO) levels both in kidney and liver. The co-treatment OTA + CURC counteracted the harmful effects of chronic OTA treatment by regulating inflammation, reducing NO levels and oxidative DNA damage in kidney and liver tissues. Histology revealed that OTA + CURC treatment determinates mainly an Iba1+ macrophagic infiltration with fewer CD3+ T-lymphocytes in the tissues. In conclusion, we evidenced that CURC exerted cytoprotective and antioxidant activities against OTA-induced toxicity in rats.