TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and several other environment/food-borne toxic compounds induce their toxicity via the aryl hydrocarbon receptor (AhR). AhR is also modulated by various endogenous ligands e.g. highly potent tryptophan (Trp)-derivative FICZ (6-formylindolo[3,2-b]carbazole) and natural ligands abundant in the human diet e.g. polyphenols. Therefore, evaluating AhR species-specific responses is crucial for understanding AhR physiological functions, establishing risk assessments, and exploring the applicability of AhR mediators in drug and food industry towards human-based usages. We studied AhR transactivation of FICZ/TCDD in vitro in a time-dependent and species-specific manner using dioxin responsive luciferase reporter gene assays derived from rat (DR-H4IIE) and human (DR-HepG2) hepatoma cells. We observed for the first time that FICZ potency was similar in both cell lines and was 40 times higher than TCDD in DR-HepG2 cells. Depleting Trp-derivative endogenously produced ligands by using culture medium without Trp, resulted in 3-fold higher AhR activation upon adding FICZ in DR-H4IIE cells, in contrast to DR-HepG2 cells which revealed a fast degradation of FICZ induction from 10 h post-exposure to complete disappearance after 24 h. Seven polyphenols and a mixture thereof, chosen based on commercially recommended doses and adjusted to human realistic exposure, caused rat and human species-specific AhR responses. Two isoflavones (daidzein and genistein) induced rat AhR synergistic effects with FICZ and/or TCDD, while quercetin, chrysin, curcumin, resveratrol, and the mixture exerted a strong inhibitory effect on the human AhR. Strikingly, resveratrol and quercetin at their realistic nanomolar concentrations acted additively in the mixture to abolish human AhR activation induced by various TCDD concentrations. Taken together, these results illustrate the species-specific complexity of AhR transcriptional activities modulated by various ligands and highlight the need for studies of human-based approaches.

The trace element fluoride can be beneficial for oral health by preventing dental caries. However, fluoride is also known as an environmental pollutant. Fluoride pollution can lead to fluoride over-ingestion and can cause health issues, including dental fluorosis. Curcumin attenuated fluoride-induced toxicity in animal models, however the molecular mechanisms of how curcumin affects fluoride toxicity remain to be elucidated. We hypothesized that curcumin attenuates fluoride toxicity through modulation of Ac-p53. Here we investigated how curcumin affects the p53-p21 pathway in fluoride toxicity.LS8 cells were treated with NaF with/without curcumin. Curcumin significantly increased phosphorylation of Akt [Thr308] and attenuated fluoride-mediated caspase-3 cleavage and DNA damage marker γH2AX expression. Curcumin-mediated attenuation of caspase-3 activation was reversed by Akt inhibitor LY294002 (LY). However, LY did not alter curcumin-mediated γH2AX suppression. These results suggest that curcumin inhibited fluoride-mediated apoptosis via Akt activation, but DNA damage was suppressed by other pathways. Curcumin did not suppress/alter fluoride-mediated Ac-p53. However, curcumin itself significantly increased Ac-p53 and upregulated p21 protein levels to suppress cell proliferation in a dose-dependent manner. Curcumin suppressed fluoride-induced phosphorylation of p21 and increased p21 levels within the nuclear fraction. However, curcumin did not reverse fluoride-mediated cell growth inhibition. These results suggest that curcumin-induced Ac-p53 and p21 led to cell cycle arrest, while curcumin attenuated fluoride-mediated apoptosis via activation of Akt and suppressed fluoride-mediated DNA damage.By inhibiting DNA damage and apoptosis, curcumin may potentially alleviate health issues caused by fluoride pollution. Further studies are required to better understand the mechanism of curcumin-induced biological effects on fluoride toxicity.

Coliform mastitis is a worldwide serious disease of the mammary gland. Curcumin is a pleiotropic polyphenol obtained from turmeric, but it is hydrophobic and rapidly eliminated from the body. However, nanoformulation of curcumin significantly improves its pharmacological activity by enhancing its hydrophobicity and oral bioavailability. Our study aimed to investigate the possible antioxidant and anti-inflammatory effects of nanocurcumin as a prophylactic against LPS-induced coliform mastitis in rat model, where LPS was extracted from a field strain of Escherichia coli (bovine mastitis isolate). The study was conducted on twenty lactating Wistar female rats divided into four equal groups, and the mastitis model was initiated by injection of LPS through the duct of the mammary gland. The results showed that nanocurcumin significantly attenuated the lipid peroxidation (MDA), oxidized glutathione, the release of pro-inflammatory cytokines (TNF-α and IL-1β), and the gene expression of TLR4, NF-κB p65, and HMGB1. Meanwhile, it improved the reduced glutathione level and Nrf2 activity and preserved the normal alveolar architecture. These findings suggested that nanocurcumin supplementation can be a promising potential protective approach for coliform mastitis.

An 8-week feeding experiment was conducted to investigate the effects of curcumin nanomicelle, curcumin, and turmeric (Curcuma longa) on growth performances, body composition, fatty acid profile, and biochemical parameters of common carp (Cyprinus carpio), and their ameliorative effects against toxicity of silver nanoparticles (AgNPs). A total of 120 healthy carps were randomly distributed into four equal treatments. Curcumin nanomicelle, curcumin, and turmeric were each added separately to the basal diet. After the feeding trials, all treatments were exposed to a non-lethal concentration of AgNPs (0.5 mg L⁻¹) for 96 h. Fish fed dietary turmeric showed a significantly higher weight gain. The body protein content was significantly increased in all feeding groups, while the lipid content showed a significant decrease in the turmeric-treated group. Dietary turmeric improved the concentration of saturated fatty acids (SFA) and monounsaturated fatty acid (MUFA). AgNP exposure led to increases in liver catalase (CAT) activity of carps fed with turmeric and curcumin. The lowest amount of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was obtained in fish fed with nanomicelle curcumin and curcumin diets. The lowest amount of silver accumulation in the liver of carps was found in fish fed with dietary curcumin nanomicelle. This experiment suggests that supplementation of turmeric (50 g kg⁻¹) or curcumin (1000 mg kg⁻¹) may play an important role in enhancing growth performances and fatty acid composition of the common carp. Moreover, administration of curcumin nanomicelle in the diet may have a potential ameliorative effect against toxicity of AgNPs.

Curcumin is a polyphenolic compound that exhibited good anticancer potential against different types of cancers through its multi-targeted effect like the termination of cell proliferation, inflammation, angiogenesis, and metastasis, thereby acting as antiproliferative and cytotoxic in nature. The present review surveys the various drug combination tried with curcumin or its synthetic analogues and also the mechanism by which curcumin potentiates the effect of almost every drug. In addition, this article also focuses on aromatherapy which is gaining much popularity in cancer patients. After thoroughly studying several articles on combination therapy of curcumin through authenticated book chapters, websites, research, and review articles available at PubMed, ScienceDirect, etc., it has been observed that multi-targeted curcumin possess enormous anticancer potential and, with whatever drug it is given in combination, has always resulted in enhanced effect with reduced dose as well as side effects. It is also capable enough in overcoming the problem of chemoresistance. Besides this, aromatherapy also proved its potency in reducing cancer-related side effects. Combining all the factors together, we can conclude that combination therapy of drugs with curcumin should be explored extensively. In addition, aromatherapy can be used as an adjuvant or supplementary therapy to reduce the cancer complications in patients.

Arsenic (As) is known for its carcinogenic and hepatorenal toxic effects causing serious health problems in human beings. Turmeric (Curcuma longa L.) extracted curcumin (Cur) is a polyphenolic antioxidant which has ability to combat hazardous environmental toxicants. This study (28 days) was carried out to investigate the therapeutic efficacy of different doses of Cur (Cur: 80, 160, 240 mg kg⁻¹) against the oxidative damage in the liver and kidney of male rats caused by sodium arsenate (Na₃AsO₄) (10 mg L⁻¹). As exposure significantly elevated the values of organ index, markers of hepatic injury (i.e., alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)) and renal functions (i.e., total bilirubin, urea and creatinine, total cholesterol, total triglycerides, and lipid peroxidation malondialdehyde (MDA)). Moreover, different antioxidant markers such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in the liver and kidney tissues were reduced after As-induced toxicity. However, Na₃AsO₄ induced histopathological changes in various organs were minimized after the treatment with Cur. The alleviation effect of Cur was dosage dependent with an order of 240>160>80 mg kg⁻¹. The oral administration of Cur prominently alleviated the As-induced toxicity in liver and kidney tissues by reducing lipid peroxidation, ALT, AST, ALP, total bilirubin, urea, creatinine, total cholesterol, total triglycerides, and low-density lipoproteins (LDL). In addition, Cur being an antioxidant improved defense system by enhancing activities of SOD, CAT, GPx, and GR. Overall, the findings explain the capability of Cur to counteract the oxidative alterations as well as hepatorenal injuries due to As intoxication.

Bisphenol A (BPA) received heightened attention in the recent years due to humans continuously being exposed to it. This study explores the effect of taurine or curcumin on subacute BPA treatment-induced nephrotoxicity in rats (Rattus norvegicus). Forty-two adult albino male rats were exposed to BPA (130 mg/kg daily) for 28 days by gastric gavage. BPA led to lipid peroxidation, inhibiting antioxidant enzyme activities like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST). BPA exposure also induced histopathological changes like tubular and glomerular degeneration, vascular congestion, and interstitial cell infiltration in kidney tissue. Cotreatment with taurine (100 mg/kg daily) or curcumin (100 mg/kg daily) alleviated the lipid peroxidation level and antioxidant enzyme activities and histological alterations brought about by BPA. In this study, curcumin and taurine application provided protection against renal toxicity caused by BPA but did not prevent toxic effect completely.

Turmeric, or Curcuma longa as it is formally named, is a multifunctional plant with numerous names. It was dubbed “the golden spice” and “Indian saffron” not only for its magnificent yellow color, but also for its culinary use. Turmeric has been utilized in traditional medicine since the dawn of mankind. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin, which are all curcuminoids, make up turmeric. Although there have been significant advancements in cancer treatment, cancer death and incidence rates remain high. As a result, there is an increasing interest in discovering more effective and less hazardous cancer treatments. Curcumin is being researched for its anti-inflammatory, anti-cancer, anti-metabolic syndrome, neuroprotective, and antibacterial properties. Turmeric has long been used as a home remedy for coughs, sore throats, and other respiratory problems. As a result, turmeric and its compounds have the potential to be used in modern medicine to cure a variety of diseases. In this current review, we highlighted therapeutic potential of curcumin and its multiple health benefits on various diseases.

Nephrotoxicity is a very important complication of 5-fluorouracil (5-FU)–treated cancer patients. Increased oxidative stress, kidney damage, and apoptosis play an important role in the pathogenesis of nephrotoxicity caused by 5-FU. In this study, protective effects of two natural compounds, hesperidin and curcumin, on experimentally induced kidney damage in mice with 5-FU were determined. Application of 5-FU resulted in severe histopathological changes and severe renal failure with increased serum urea and creatinine levels. Also, 5-FU–induced kidney damage, increased levels of malondialdehyde (MDA), decreased superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and glutathione (GSH) level have been demonstrated. Also, where 5-FU is in the concentration of caspase-3 and 8-OHdG immune-positive cells and therefore causes apoptosis and DNA damage in kidney tissue cells. However, especially high doses of hesperidin and curcumin treatment significantly improved 5-FU–induced oxidative stress/lipid peroxidation, apoptosis/DNA damage, and renal dysfunction. Based on these data, our results suggest that hesperidin and curcumin may be used as new and promising agents against 5-FU–induced nephrotoxicity.

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (HAPNPs), a prospective nano-biomaterial, is extensively studied, its interaction on the reproductive system following exposure is less exploited. In the present study, male rats were exposed to HAPNPs (300 mg/kg BW) to determine its possible reproductive toxicity. Also, the protective effects of chitosan (CSNPs, 280 mg/kg BW) and/or curcumin (CurNPs, 15 mg/kg BW) nanoparticles against HAPNPs-induced reproductive toxicity were studied. Animals were orally gavage daily with respective doses for 45 consecutive days. The obtained results indicated that HAPNPs caused a significant decrease in sperm count, sperm motility, testosterone hormone, steroidogenic enzymes (17-ketosteroid reductase and 17β-hydroxysteroid dehydrogenase), and antioxidant enzymes (glutathione peroxidase, glutathione S-transferase, catalase, and superoxide dismutase) in addition to total antioxidant capacity and reduced glutathione. LH and FSH, abnormal sperm, oxidative stress parameters (thiobarbituric acid-reactive substances (TBARS), nitric oxide (NO), and 8-hydroxy-deoxyguanosine (8-OHdG)), p53, TNFα, and interleukin-6 were significantly increased. The DNA damage was also analyzed by assaying 8-OHdG level which is considered as an indicator of genotoxicity and also suppression of the gene expression of mtTFA, induction of UCP2. Similarly, the histopathological evaluation was also changed following exposure to HAPNPs. The antioxidant activity of CSNPs and CurNPs showed mitigating effect against reproductive deterioration induced by HAPNPs throughout improvements in semen characteristics, sex hormones, inflammatory factors, and antioxidant status. The present study concluded that HAPNPs induced reproductive toxicity and it is important to use nano-antioxidants CSNPs and CurNPs as protective agents.