A Direct Link Implicating Loss of SLC26A6 to Gut Microbial Dysbiosis, Compromised Barrier Integrity and Inflammation.

BACKGROUND: Putative anion transporter-1 (PAT1, SLC26A6) plays a key role in intestinal oxalate and bicarbonate secretion. PAT1 knockout (PKO) mice exhibit hyperoxaluria and nephrolithiasis. Notably, diseases such as inflammatory bowel diseases (IBD) are also associated with higher risk of hyperoxaluria and nephrolithiasis. However, the potential role of PAT1 deficiency in gut barrier integrity and susceptibility to colitis is currently elusive. METHODS: Age-matched PKO and wild-type (WT) littermates were administered 3.5%-DSS in drinking water for 6 days. Ileum and colon of control and treated mice were harvested. mRNA and protein expression of tight junction (TJ) proteins were determined by RT-PCR and western blotting. Severity of inflammation was assessed by measuring diarrheal phenotype, cytokine expression and H&E staining. Gut microbiome and associated metabolome were analyzed by 16S rRNA sequencing and mass spectrometry, respectively. RESULTS: PKO mice exhibited significantly higher loss of body weight, gut permeability, colonic inflammation, and diarrhea in response to DSS treatment. Additionally, PKO mice showed microbial dysbiosis and significantly reduced levels of butyrate and butyrate-producing microbes compared to controls. Cohousing WT and PKO mice for 4 weeks resulted in PKO-like signatures on the expression of TJ proteins in the colon of WT mice. CONCLUSION: Our data demonstrate that loss of PAT1 disrupts gut microbiome and related metabolites, decreases gut barrier integrity, and increases host susceptibility to intestinal inflammation. These findings, thus, highlight a novel role of the oxalate transporter PAT1 in promoting gut barrier integrity and its deficiency appears to contribute to the pathogenesis of IBD.

Evaluation of the efficacy and safety of a herbal formulation for rheumatoid arthritis - A non-inferiority randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a diverse disease characterized by a variable, progressive course of articular and extra-articular symptoms that are linked with pain, disability, and mortality. The exact cause of rheumatoid arthritis is still being investigated, and there is no cure for this debilitating, persistent, painful disease. Qurs-e-Mafasil, a herbal Unani preparation, is regarded as a potent treatment for Waja'al-Mafasil, a condition clinically similar to rheumatoid arthritis, but scientific evidence is scarce. AIM OF THE STUDY: This study aimed to assess the non-inferiority of Qurs-e-Mafasil compared to celecoxib in the treatment of patients with rheumatoid arthritis. MATERIALS AND METHODS: This randomized controlled trial was conducted on seventy patients diagnosed with rheumatoid arthritis between the ages of 35 and 55 years. The participants were randomly allocated in a ratio of 3:2, with 42 participants in the test group and 28 participants in the control group. The test group was administered 2 tablets (each having 500 mg) of Qurs-e-Mafasil, while the control group was administered 1 capsule of Celecoxib 100 mg. Both medications were delivered for four weeks. The primary outcome measure was European League Against Rheumatism (EULAR) response criteria based on Disease Activity Score-28 (DAS28) assessed before and after therapy, whereas the secondary outcome measure was the change in joint pain severity as determined by a 100 mm Visual Analog Scale (VAS) at baseline and each follow-up. The safety of the interventions was evaluated based on adverse event monitoring at each follow-up and laboratory tests including hemogram, Liver Function Tests (LFTs), Kidney Function Tests (KFTs), and a complete urine examination performed at baseline and after four weeks of treatment. RESULTS: The per-protocol analysis was done on 50 participants (30 in test group and 20 in control group) who completed the study duration. Thus, at the conclusion of the trial, participants in the test and control groups had either a moderate or no response based on EULAR response criteria. The odds ratio for no response versus moderate response between the test and the control groups was 0.71 (95% CI: 0.20-2.55) with p = 0.744. Moreover, the observed mean differences in VAS scores between the test and the control groups at 1st, 2nd, 3rd, and final follow-up were -0.33 (95% CI: -6.65 to 5.99, p = 0.916), 0.50 (95% CI: -5.63 to 6.63, p = 0.870), 2.42 (95% CI: -2.95 to 7.78, p = 0.370), and 3.00 (95% CI: -1.82 to 7.84, p = 0.219), respectively. CONCLUSIONS: The differences in primary and secondary outcomes between the two groups indicate that Qurs-e-Mafasil, a herbal Unani formulation containing Zingiber officinale Roscoe rhizome, Colchicum luteum Baker root, Piper nigrum L. fruit, and Withania somnifera (L.) Dunal. root, is comparable to celecoxib in the treatment of rheumatoid arthritis.

Evaluation of the efficacy of hydro-alcoholic extract of Evolvulus alsinoides L. for the treatment of primary hypertension - A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Evolvulus alsinoides L. (Sankhaholi) has been traditionally used in Unani (Greco-Arabic) medicine to treat diverse cardiovascular disorders. Notably, preclinical and clinical investigations have substantiated its remarkable potential as an antihypertensive agent. AIM OF THE STUDY: The aim of this study was to compare the efficacy of hydroalcoholic extract of Evolvulus alsinoides L. and ramipril in treating hypertension using a higher dose of the test drug within the recommended limit. MATERIALS AND METHODS: In this open-label randomized controlled trial, 57 participants (29 in the test group, 28 in the control group) completed the 42-day study. The test group received 630 mg of dried hydro-alcoholic extract of Evolvulus alsinoides L. in capsule form orally once daily, while the control group received 5 mg of Ramipril orally once daily. Participants in both groups were advised to adhere to the Dietary Approaches to Stop Hypertension (DASH) eating plan in terms of diet and lifestyle adjustments recommended by JNC-8. The primary outcome measures were changes in systolic and diastolic blood pressure as well as changes in plasma levels of hsCRP and IL6. Secondary outcome measures included changes in symptoms such as palpitations, giddiness, headaches, fatigue and shortness of breath. Headaches, palpitations, and giddiness were assessed using a customized Visual Analog Scale (VAS) graded as "none," "mild," "moderate," and "severe". Fatigue was assessed on a binary scale as either absent or present, and dyspnea was assessed using the modified Medical Research Council (mMRC) scale for breathlessness. Both primary and secondary outcomes were assessed at baseline and each follow-up visit (2nd week, 4th week, and 6th week) until the completion of the trial. RESULTS: At the end of the trial, the mean differences for the primary outcomes were as follows:SBP:-1.8895%CI:-4.82,1.05,p=0.203,d=0.33, DBP: -2.8395%CI:-4.67,-0.10,p=0.003,d=0.8, hsCRP: -1.4095%CI:-2.80,-0.003,p=0.49,d=0.53, and IL6: -88.6795%CI:-148.90,-28.43,p=0.005,d=0.78. No statistically significant differences were observed between the two groups for any of the secondary outcomes. CONCLUSIONS: Based on the preliminary results, it can be inferred that the hydro-alcoholic extract of Evolvulus alsinoides L. exhibits significant antihypertensive potential, comparable to that of ramipril. Furthermore, it appears that Evolvulus alsinoides L. may be more effective than ramipril in reducing the biochemical markers of inflammation associated with primary hypertension. However, additional research is required to validate these findings.

A comprehensive review on Trigonella foenum-graecum L. with special reference to Unani medicine.

Trigonella foenum-graecum L., commonly known as Hulba or Methi in Unani medicine, is an annual self-pollinating plant belonging to the Leguminosae family. It has been utilized for centuries to treat a wide range of diseases, and modern research has supported its traditional medicinal claims. In this study, the authors have conducted manual and online searches to gather and summarize the scientific literature on Hulba. This article seeks to underscore the potential of Hulba in addressing a variety of health conditions as identified by esteemed classical Unani scholars, as well as to investigate its phytochemistry and pharmacological properties in contemporary medicine. The authors have utilized electronic databases, such as PubMed, Science Direct, DOAJ, Google Scholar, and Ayush Research Portal to filter published material. According to the gathered literature, Unani physicians have consistently recommended Hulba seeds for a variety of ailments, such as indigestion, flatulence, colitis, arthritis, backache, paralysis, headaches, common cold, cough, bronchial asthma, diabetes mellitus, vitiligo, and pityriasis. Additionally, the seeds and green leaves of Hulba contain several chemical constituents, such as alkaloids, flavonoids, steroids, saponins, and amino acids. Furthermore, several pharmacological studies have demonstrated that Hulba possesses various properties, including antidiabetic, antispasmodic, hypolipidemic, immunological, antibacterial, anthelmintic, anti-inflammatory, analgesic, and antioxidant activities. Based on the available evidence, it can be concluded that Hulba has been effectively used in Unani medicine for treating a wide range of diseases. Unani scholars have extensively documented its pharmacological properties, which have been supported by modern research studies. However, further research is necessary to validate some of the claims made in traditional medicine using scientific parameters.

Evaluation of the efficacy of topical Terminalia chebula Retz. with vinegar in the treatment of tinea corporis: a non-inferiority randomized controlled trial.

OBJECTIVES: Unani physicians have suggested a wide range of anti-dermatophytic remedies, although the scientific evidence is scarce. Thus, the efficacy and safety of Terminalia chebula Retz. fruit powder mixed with vinegar was compared with terbinafine hydrochloride 1% cream in the treatment of tinea corporis in order to establish the non-inferiority of test drugs. METHODS: The primary outcome measures were change in the presence or absence of hyphae on KOH mount test, change in pruritus severity assessed on 100 mm VAS and change in physician's global assessment. Secondary outcome measure was change in the dermatology life quality index (DLQI). Hemograms, serum creatinine, serum bilirubin, and random blood sugar levels were measured at the baseline and after treatment to ensure the safety of the interventions. RESULTS: A per-protocol analysis was done on 40 participants (21 in the test group and 19 in the control group). The observed differences in the primary and secondary outcomes between the test and control groups were greater than the non-inferiority margin, signifying that the test drugs were not inferior. CONCLUSIONS: It may be inferred that the trial drug Terminalia chebula Retz. fruit powder mixed with vinegar is not inferior to terbinafine hydrochloride cream in the treatment of tinea corporis.

The Efficacy and Safety of Herbal Unani Formulations in Chronic Plaque Psoriasis: A Single-arm Clinical Trial.

Background: Despite there being advanced treatment options, psoriasis remains an incurable and recurring disease. Noteworthy scholars of Unani (Greco-Arab) medicine have proposed many drugs and formulations for psoriasis but the scientific evidence on the same is scarce. Hence, trial formulations were selected for the study. Primary Study Objectives: This study was designed to evaluate the efficacy and safety of two herbal Unani formulations, Ma΄jun Mundi and Qairuti Karnab, in the management of chronic plaque psoriasis (CPP). Methods/Design: This open-label, single-arm clinical trial was conducted on 33 participants, of whom 30 completed the 12-week treatment course. Setting: This study was conducted at the Central Research Institute of Unani Medicine (CRIUM), Hyderabad, Telangana, India, from 01 August 2018 to 25 May 2019. Participants: Participants of any gender aged 18 to 65 years with clinically diagnosed CPP and psoriasis area severity index (PASI) ≥ 10% were included in the trial. Interventions: The participants received 5 g of Ma΄jun Mundi (a semisolid preparation) orally, twice daily with water, followed by the topical application of Qairuti Karnab (a homogenous paste) to cover the lesions over 12 weeks. Outcome Measures: The primary outcome measure was the change in PASI determined pre- and post-trial in terms of mean and percentage reduction. Secondary outcome measures were changes in patient global assessment (PGA) on a 100 mm visual analog scale, investigator global assessment (IGA) on a 6-point scale, and subjective parameters including erythema, induration, scaling, and itchiness. Results: The analysis revealed a significant reduction in the PASI score, with 12 subjects (40%) achieving PASI 75 and 3 subjects (10%) achieving PASI 90. Significant improvements were also observed in secondary outcome measures with no adverse events. Conclusion: The findings of the study indicate that the trial formulations exhibit a notable anti-psoriatic effect without any adverse effects. The formulations are worthy of further evaluation as an alternative treatment for CPP.

The efficacy and safety of dry cupping in cervical spondylosis with optimization of cup application time - a randomized clinical trial.

OBJECTIVES: Dry cupping therapy (DCT) is considered beneficial in the amelioration of cervical spondylosis (CS) symptoms in Unani medicine. Therefore, the focus of this study was to ascertain the efficacy of DCT and optimal cup application time duration for CS. METHODS: It was a randomized clinical trial involving 45 participants with clinically diagnosed CS. The eligible subjects were randomly categorized into three groups, each having 15 participants. Each of the three groups, i.e., A, B, and C, received DCT daily for 15 days for 8 min, 10 min, and 12 min, respectively. All the participants were evaluated at the baseline, 7th, and 15th days of the trial using the neck disability index (NDI) as well as the visual analogue scale (VAS). RESULTS: The baseline mean ± SD of NDI and VAS scores were significantly reduced in all the three groups at the end of the trial. Although all three groups were statistically equal in terms of NDI, group-C demonstrated greater efficacy in terms of VAS. CONCLUSIONS: The per-protocol analysis showed that dry cupping effectively alleviated neck pain across all treatment groups. Although, this effect on neck disability index was statistically equal in all three groups, the 12-min protocol was more successful in reducing pain.

The Efficacy of Kundur (Boswellia serrata Roxb. Ex Colebr.) in Vulvovaginal Candidiasis: A Randomized Control Trial.

Context: Kundur, Boswellia serrata Roxb. ex Colebr., is prescribed by Unani (Greco-Arab) scholars clinically under conditions similar to vulvovaginal candidiasis (VVC) and has been supported by recent pharmacological studies, but scientific evidence is scarce. Objectives: The study intended to investigate the drug's scientific parameters and to compare its efficacy and safety to that of Miconazole nitrate (2% w/w) in treatment of VVC. Design: The research team designed a randomized controlled trial (RCT). Setting: The RCT was performed in the Department of Ilmul Qabalat wa Amraze Niswan at Luqman Unani Medical College Hospital and Research Center in Vijaypura, India, between November 2018 and March 2020. Participants: Participants were 40 married women, aged 18 to 45 years, who had been clinically examined and diagnosed with VVC. Interventions: Participants were randomly allocated to the Boswellia serrata (Kundur) group, the intervention group (n = 20), or to the miconazole group, the control group (n = 20). The Kundur group took a one-gram tablet of Kundur as a vaginal insert every day at bedtime for 21 days, while the control group used vaginal suppositories with 100 mg of miconazole (2% w/w) every day at bedtime for seven days. Outcome Measures: The primary outcome measures were changes: (1) in vulval itching (pruritus), (2) in vaginal discharge, (3) in painful urination (dysuria), (4) in recurrent genital pain (dyspareunia), and (5) in quality of life (QoL). The secondary outcome measures were mycological clearing on a potassium hydroxide (KOH) test and a per-speculum pelvic examination for the presence or absence of curdy discharge, vulval erythema, and vulval swelling. Results: The response to the intervention was greater than that of the control in reducing pruritus vulvae and vaginal discharge. However, both drugs were equally effective in improving the rest of the parameters, including QoL. Conclusion: The VVC symptoms were equally and significantly improved in both the intervention and the control groups, and Boswellia serrata Roxb. ex Colebr. was shown to be efficacious in the management of VVC. Further studies with a rigorous design and larger sample size are needed to reinforce scientific evidence.

A non-inferiority randomized controlled clinical trial comparing Unani formulations and PUVAsol in non-segmental vitiligo.

OBJECTIVES: Greco-Arab medicine is an ancient system of medicine with greater treasure on therapeutics of vitiligo. The trial Unani formulations have not been scientifically explored for their safety and efficacy, but have been repeatedly prescribed by the great Unani physicians in the management of Baras (vitiligo). Hence, these interventions were selected for the trial. METHODS: In this randomized, controlled, open-label clinical trial, 82 participants with non-segmental vitiligo aged 18-40 years were block randomized to either receive Unani interventions or control for 16 weeks. Out of 82 participants, 42 were randomized to the Unani group and 40 were randomized to the control group. The primary outcome measure was change in vitiligo area scoring index (VASI), which was assessed on weeks 4, 8, 12 and 16. The secondary outcome measures included the patient's global assessment on VAS and investigator's global assessment based on photographic evaluation at baseline and after the treatment. Safety parameters included hemogram, LFTs, RFTs, CXR, ECG, urine, and stool examinations, which were evaluated at baseline and after the treatment. RESULTS: The per-protocol analysis was done on 30 participants in each group and the response in Unani group was not inferior to those receiving control group. The mean ± SD of vitiligo area scoring index (VASI) decreased from 4.09 ± 2.87 and 5.50 ± 5.73 at baseline to 3.13 ± 2.20 and 4.29 ± 4.95 at the end of the trial in both the Unani and control groups respectively. CONCLUSIONS: The study inferred that both the interventions are equally effective and well-tolerated in patients with non-segmental vitiligo.

Oral Administration of Copper Chloride Damages DNA, Lowers Antioxidant Defense, Alters Metabolic Status, and Inhibits Membrane Bound Enzymes in Rat Kidney.

Copper (Cu) is a heavy metal that is widely used in industries and is also an essential micronutrient for living beings. However, excess Cu is toxic and human exposure to high levels of this metal results in numerous adverse health effects. We have investigated the effect of oral administration of copper chloride (CuCl2), a Cu(II) compound, on various parameters of oxidative stress, cellular metabolism, and DNA integrity in the rat kidney. This was done to delineate the molecular mechanism of Cu(II) toxicity. Adult male rats were randomly divided into five groups. Animals in four CuCl2-treated groups were separately administered single acute oral dose of CuCl2 at 5, 15, 30, and 40 mg/kg body weight. Animals in the fifth group were not given CuCl2 and served as the control. All rats were sacrificed 24 h after the dose of CuCl2 and their kidneys removed. CuCl2 administration led to significant alterations in enzymatic and non-enzymatic parameters of oxidative stress. It changed the activities of metabolic and membrane bound enzymes and also decreased the activities of brush border membrane enzymes. CuCl2 treatment dose-dependently enhanced DNA damage and DNA-protein crosslinking in renal cells, when compared to the control group. The administration of CuCl2 also resulted in marked morphological changes in the kidney, with more prominent alterations at higher doses of CuCl2. These results clearly show that CuCl2 impairs the antioxidant defense system resulting in oxidative damage to the kidney.

MiR-539-3p impairs osteogenesis by suppressing Wnt interaction with LRP-6 co-receptor and subsequent inhibition of Akap-3 signaling pathway.

X-linked hypophosphatemia (XLH), an inheritable form of rickets is caused due to mutation in Phex gene. Several factors are linked to the disease's aetiology, including non-coding RNA molecules (miRNAs), which are key post-transcriptional regulators of gene expression and play a significant role in osteoblast functions. MicroRNAs sequence analysis showed differentially regulated miRNAs in phex silenced osteoblast cells. In this article, we report miR-539-3p, an unidentified novel miRNA, in the functional regulation of osteoblast. MiR-539-3p overexpression impaired osteoblast differentiation. Target prediction algorithm and experimental confirmation by luciferase 3' UTR reporter assay identified LRP-6 as a direct target of miR-539-3p. Over expression of miR-539-3p in osteoblasts down regulated Wnt/beta catenin signaling components and deteriorated trabecular microarchitecture leading to decreased bone formation in ovariectomized (Ovx) mice. Additionally, biochemical bone resorption markers like CTx and Trap-5b were elevated in serum samples of mimic treated group, while, reverse effect was observed in anti-miR treated animals along with increased bone formation marker P1NP. Moreover, transcriptome analysis with miR-539-3p identified a novel uncharacterized Akap-3 gene in osteoblast cells, knock down of which resulted in downregulation of osteoblast differentiation markers at both transcriptional and translational level. Overall, our study for the first time reported the role of miR-539-3p in osteoblast functions and its downstream Akap-3 signalling in regulation of osteoblastogenesis.

Treatment of chronic plaque psoriasis with herbal Unani formulations: A randomized control trial of efficacy and safety.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis, despite modern therapeutic options, is incurable and recurrent. In Unani (Greco-Arab) medicine, many medications and formulations have been prescribed by eminent scholars for conditions clinically similar to psoriasis, though empirical evidence is sparse. Hence, the experimental formulations ItrifalShahtra and MarhamHina were chosen to be compared to the standard therapies PUVAsol and petrolatum for their safety and efficacy. MATERIALS AND METHODS: This open-label, randomized control clinical trial was conducted on 66 male and female participants with chronic plaque psoriasis, ranging in age from 18 to 65 years. In each group, 33 participants were block randomized to either receive Unani formulations or control drugs for 12 weeks. The Unani group received oral Itrifal Shahtra (a semisolid paste) and topical MarhamHina (an ointment) twice daily, and the control group received oral 8-methoxypsoralen and topical petroleum jelly for local application. Participants of both groups were advised to get daily sunlight exposure for 5-15 min. The primary outcome measure was the change in psoriasis area and severity index (PASI) assessed at each visit. Secondary outcome measures were patient global assessment on a 100 mm VAS applied at baseline and after 12 weeks of treatment and change in subjective parameters including erythema, induration, scaling, and itching, assessed on a 5-point scale at every visit. Hemogram, LFTs, RFTs, CXR, ECG, urine, and stool tests were all assessed at baseline and after treatment for the safety of the drugs. RESULTS: The per-protocol analysis was done on 25 participants in each group. The mean ± SD of the psoriasis area severity index (PASI) significantly decreased from 27.88 ± 12.01 and 23.61 ± 9.79 at baseline to 5.01 ± 4.59 and 9.85 ± 7.16 after completion of the trial therapies in both Unani and control groups, respectively. Also, the test formulations outperformed the control drugs on clinically significant endpoints, PASI 50 and PASI 75, with all 25 participants achieving PASI 50 and 76% achieving PASI 75. CONCLUSION: The trial formulations, ItrifalShahtra and MarhamHina may be superior to control drugs PUVAsol and petrolatum in terms of safety, efficacy, and tolerability in the treatment of chronic plaque psoriasis. Thus, the Unani formulations may further be evaluated in a well-designed multicentric superiority trial with an adequate sample size.

The efficacy of topical Marham-e-Akbar in chronic atopic dermatitis - an open-label interventional study.

OBJECTIVES: Chronic atopic dermatitis (AD) is an inflammatory skin condition marked by intense pruritus, dry skin, and severe impact on the life quality of the patients. Conventionally, it is managed by using emollients, calcineurin inhibitors, and topical corticosteroids. In Unani medicine, eminent scholars advocated many drug formulations including topical Marham-e-Akbar for effective healing of AD but scientific evidence is scarce. Hence, this study was designed. METHODS: This was a single-arm clinical trial conducted on 30 participants aged 18-65 years suffering from chronic AD after obtaining written informed consent. The trial intervention was Marham-e-Akbar consisting of Murdar Sang (Plumbi oxidum); Sindur (red lead); olive oil (Olea europaea oil); Kath (Acacia catechu extract); Safeda Kashgari (Zinc oxide); Sirka (vinegar); and Phitkiri (alum) to be applied twice daily for 42 days. The objective parameters were SCORAD and DLQI, while the subjective parameters included itching, scaling, and erythema assessed on a customized VAS scale and 4-point Likert scale. RESULTS: The pre-post analysis inferred statistically significant attenuation in subjective parameters (itching, scaling, and erythema) and objective scales (SCORAD) and (DLQI) with p<0.001. CONCLUSIONS: The study findings deduced that Marham-e-Akbar is effective in the amelioration of chronic atopic dermatitis and quality of life of the patients as well.

Copper chloride inhibits brush border membrane enzymes, alters antioxidant and metabolic status and damages DNA in rat intestine: a dose-dependent study.

Copper (Cu) is an extensively used heavy metal and an indispensible micronutrient for living beings. However, Cu is also toxic and exerts multiple adverse health effects when humans are exposed to high levels of this metal. We have examined the effect of single acute oral dose of copper chloride (CuCl2) on parameters of oxidative stress, cellular metabolism, membrane and DNA damage in rat intestine. Adult male Wistar rats were divided into four groups and separately administered a single oral dose of 5, 15, 30 and 40 mg CuCl2/kg body weight. Rats not administered CuCl2 served as the control. Oral administration of CuCl2 led to significant alterations in the activities of metabolic and membrane-bound enzymes; brush border enzymes were inhibited by 45-75% relative to the control set. Inhibition of antioxidant enzymes diminished the metal-reducing and free radical quenching ability of the cells. Oxidative damage caused cellular oxidation of thiols, proteins and lipids. Diphenylamine and comet assays showed that CuCl2 treatment enhanced DNA damage while DNA-protein crosslinking was also increased in the intestinal cells. Examination of stained sections showed that CuCl2 treatment led to marked histological changes in the intestine. All the changes seen were in a CuCl2 dose-dependent manner with more prominent alterations at higher doses of CuCl2. These results clearly show that oral administration of CuCl2 results in oxidative damage to the intestine which can impair its digestive and absorptive functions.

Mitigation of Cu(II)-induced damage in human blood cells by carnosine: An in vitro study.

Copper (Cu) is an essential micronutrient but human exposure to high level of this metal results in adverse health effects. Oxidative stress is assumed to play a major role in the mechanism of Cu-induced toxicity. The protective role of carnosine, an antioxidant and antiglycating agent, was examined against Cu-induced toxicity in isolated human blood cells. Red blood cells (RBC) were treated with 0.5 mM copper chloride (CuCl2), a Cu(II) compound, either alone or after treatment with carnosine. Incubation of RBC with CuCl2 increased protein oxidation, lipid peroxidation, methemoglobin formation and lowered glutathione content. The antioxidant defense system was impaired and production of reactive oxygen (ROS) and reactive nitrogen species (RNS) was enhanced. Pre-incubation of RBC with carnosine protected the cells against CuCl2-induced oxidative damage. It restored the activities of several antioxidant, membrane-bound and metabolic enzymes, decreased the generation of ROS and RNS, enhanced the antioxidant power of cells and prevented inactivation of plasma membrane redox system. Carnosine also protected human lymphocytes from CuCl2-induced DNA damage. The protective effects of carnosine were concentration-dependent while carnosine itself did not exhibit any adverse effect. Carnosine can, therefore, be used as a possible chemoprotectant against the harmful effects of this extremely redox active metal.

Taurine attenuates Cr(VI)-induced cellular and DNA damage: an in vitro study using human erythrocytes and lymphocytes.

Hexavalent chromium [(Cr(VI)] is widely used in several industries, but human exposure results in multiple organ toxicity. Enhanced generation of free radicals and reactive species is thought to play a key role in Cr(VI)-induced toxicity. We have examined the effect of taurine, a simple sulphur-containing amino acid and an antioxidant, on potassium dichromate [K2Cr2O7, a Cr(VI) compound]-induced cytotoxicity and genotoxicity in human blood cells. Erythrocytes were treated with K2Cr2O7, either alone or after incubation with different concentrations of taurine. Treatment of erythrocytes with K2Cr2O7 alone led to marked increase in generation of reactive oxygen and nitrogen species, lipid and protein oxidation. This was accompanied by decrease in total sulfhydryl and glutathione content and lowered antioxidant power of the cells. This suggests that Cr(VI) induces oxidative stress in the cells. Incubation of erythrocytes with taurine prior to addition of K2Cr2O7, resulted in a concentration-dependent decrease in the generation of reactive oxygen and nitrogen species, mitigation of oxidative stress and amelioration of antioxidant power of these cells. It also restored the activities of several metabolic, antioxidant and membrane-bound enzymes. Cr(VI)-induced damage to erythrocyte membrane and lymphocyte DNA was also significantly attenuated by prior administration of taurine. These results suggest that taurine can function as a chemoprotectant against Cr(VI)-induced oxidative injury and can be potentially used to mitigate the toxic effects of this transition metal ion.

Copper(II) generates ROS and RNS, impairs antioxidant system and damages membrane and DNA in human blood cells.

Copper (Cu) is widely used in various industries, and human exposure to this metal results in severe multi-organ toxicity, which is thought to be due to the generation of free radicals by Fenton-like reaction. The generation of reactive oxygen as well as nitrogen species and free radicals results in induction of oxidative stress in the cell. We have studied the effect of different concentrations of Cu(II) on human erythrocytes and lymphocytes. Incubation of erythrocytes with copper chloride, a Cu(II) compound, enhanced the production of reactive oxygen and nitrogen species, decreased glutathione and total sulphydryl content and increased protein oxidation and lipid peroxidation. All changes were in a Cu(II) concentration-dependent manner. This strongly suggests that Cu(II) causes oxidative damage in erythrocytes. The activities of major antioxidant enzymes were altered, and antioxidant power was lowered. Cu(II) treatment also resulted in membrane damage in erythrocytes as seen by electron microscopy and lowered activities of plasma membrane-bound enzymes. Incubation of human lymphocytes with Cu(II) resulted in DNA damage when studied by the sensitive comet assay. These results show that Cu(II) exerts cytotoxic and genotoxic effects on human blood cells probably by enhancing the generation of reactive oxygen and nitrogen species.

Bougainvillea flower extract mediated zinc oxide's nanomaterials for antimicrobial and anticancer activity.

The zinc oxide nanomaterials (ZnO-NMs), owing to their broad biomedical applications have lately attracted the incredible interest in the development of therapeutic agents against microbial infections. In this contribution, we have biosynthesized ZnO-NMs with a size of ˜ 40 nm from the Bougainvillea flower extracts. The FTIR and SEM-EDX mapping analysis confirmed the size, shape and biogenic origin of ZnO-NPs. Furthermore, the purified ZnO-NMs were applied for antibacterial studies against susceptible and resistant bacterial strains and to elucidate the possible mechanism of their activity. The XTT assay and confocal imaging confirmed the ZnO-NMs materials anti-biofilm activities against medically important pathogens, i.e., S. aureus and E. coli. Moreover, the absence of cytotoxicity against healthy kidney cells (HEK-293) and erythrocytes confirmed their biocompatible nature. Furthermore, the biosynthesized ZnO-NMs showed potent anticancer activity against the breast cancer cell line (MCF-7). These biosynthesized ZnO-NMs are having excellent antimicrobial and anticancer activities and are highly biocompatible due to biogenic nature. During antimicrobial study, Zno-NMs showed excellent minimum inhibitory concentration 16 µg concentration againt E. coli, P. aeruginosa and S. aureus. While in anticancer activity, of ZnO-NMs with 15 µg/ml dose showed good response against MCF-7 cell line. Further, this killing was mechanically confirmed by ROS generation by the ZnO-NMs, which cause cell lysis by the peroxidation of membrane lipid. So, this biogenic ZnO-NMs can be used in the future for nanomaterial-based drug development.

3,4-Dihydroxybenzaldehyde quenches ROS and RNS and protects human blood cells from Cr(VI)-induced cytotoxicity and genotoxicity.

Hexavalent chromium [Cr(VI)] is the most toxic and potent form of chromium and induces multiple organ damage in humans and experimental animals. Oxidative stress has been implicated in the toxicity of Cr(VI). We have examined the potential role of 3,4-dihydroxybenzaldehyde (DHB), a plant polyphenolic antioxidant, in protecting human erythrocytes and lymphocytes from Cr(VI)-induced cytotoxicity and genotoxicity. Erythrocytes were treated with potassium dichromate, a Cr(VI) compound, in presence and absence of DHB. Incubation of erythrocytes with Cr(VI) enhanced the generation of reactive oxygen and nitrogen species, increased lipid and protein oxidation, methemoglobin levels, and lowered antioxidant power of cells. However, prior treatment of erythrocytes with DHB, resulted in a significant DHB dose-dependent decrease in reactive oxygen and nitrogen species levels and restoration of oxidative stress parameters. DHB also improved the antioxidant power of erythrocytes and restored the activities of major antioxidant, metabolic and membrane bound enzymes. Electron microscopic studies images DHB prevented Cr(VI)-induced morphological changes in erythrocytes. The single cell gel electrophoresis assay showed that DHB mitigated Cr(VI)-induced DNA damage in lymphocytes. These results clearly show that DHB protects human blood cells from Cr(VI)-induced oxidative damage and can be potentially used in reducing the toxic effects of this metal ion.

Hexavalent chromium induces reactive oxygen species and impairs the antioxidant power of human erythrocytes and lymphocytes: Decreased metal reducing and free radical quenching ability of the cells.

The toxicity of hexavalent chromium [Cr(VI)] in biological systems is thought to be closely associated with the generation of free radicals and reactive oxygen species. These species are produced when Cr(VI) is reduced to its trivalent form in the cell. This process results in oxidative stress due to an imbalance between the detoxifying ability of the cell and the production of free radicals. We have studied the effect of potassium dichromate (K2Cr2O7), a [Cr(VI)] compound, on the antioxidant power of human erythrocytes and lymphocytes under in vitro conditions. Incubation of erythrocytes and lymphocytes with different concentrations of K2Cr2O7 resulted in a marked dose-dependent decrease in reduced glutathione and an increase in oxidized glutathione and reactive oxygen species levels. The antioxidant power of the cells was decreased, as determined by metal reducing and free radical quenching assays. These results show that [Cr(VI)] upregulates the generation of reactive oxygen species and, as a consequence, the cellular antioxidant defences are compromised. The resulting oxidative stress may contribute to Cr(VI)-induced cellular damage.