Deciphering the molecular mechanism of NLRP3 in BPA-mediated toxicity: Implications for targeted therapies.

Bisphenol-A (BPA), a pervasive industrial chemical used in polymer synthesis, is found in numerous consumer products including food packaging, medical devices, and resins. Detectable in a majority of the global population, BPA exposure occurs via ingestion, inhalation, and dermal routes. Extensive research has demonstrated the adverse health effects of BPA, particularly its disruption of immune and endocrine systems, along with genotoxic potential. This review focuses on the complex relationship between BPA exposure and the NOD-like receptor protein 3 (NLRP3) inflammasome, a multiprotein complex central to inflammatory disease processes. We examine how BPA induces oxidative stress through the generation of intracellular free radicals, subsequently activating NLRP3 signaling. The mechanistic details of this process are explored, including the involvement of signaling cascades such as PI3K/AKT, JAK/STAT, AMPK/mTOR, and ERK/MAPK, which are implicated in NLRP3 inflammasome activation. A key focus of this review is the wide-ranging organ toxicities associated with BPA exposure, including hepatic, renal, gastrointestinal, and cardiovascular dysfunction. We investigate the immunopathogenesis and molecular pathways driving these injuries, highlighting the interplay among BPA, oxidative stress, and the NLRP3 inflammasome. Finally, this review explores the emerging concept of targeting NLRP3 as a potential therapeutic strategy to mitigate the organ toxicities stemming from BPA exposure. This work integrates current knowledge, emphasizes complex molecular mechanisms, and promotes further research into NLRP3-targeted interventions.

Computational Analysis of Non-synonymous SNPs in ATM Kinase: Structural Insights, Functional Implications, and Inhibitor Discovery.

Ataxia telangiectasia-mutated (ATM) protein kinase, a key player in cellular integrity regulation, is known for its role in DNA damage response. This study investigates the broader impact of ATM on cellular processes and potential clinical manifestations arising from mutations, aiming to expand our understanding of ATM's diverse functions beyond conventional roles. The research employs a comprehensive set of computational techniques for a thorough analysis of ATM mutations. The mutation data are curated from dbSNP and HuVarBase databases. A meticulous assessment is conducted, considering factors such as deleterious effects, protein stability, oncogenic potential, and biophysical characteristics of the identified mutations. Conservation analysis, utilizing diverse computational tools, provides insights into the evolutionary significance of these mutations. Molecular docking and dynamic simulation analyses are carried out for selected mutations, investigating their interactions with Y2080D, AZD0156, and quercetin inhibitors to gauge potential therapeutic implications. Among the 419 mutations scrutinized, five (V1913C, Y2080D, L2656P, C2770G, and C2930G) are identified as both disease causing and protein destabilizing. The study reveals the oncogenic potential of these mutations, supported by findings from the COSMIC database. Notably, Y2080D is associated with haematopoietic and lymphoid cancers, while C2770G shows a correlation with squamous cell carcinomas. Molecular docking and dynamic simulation analyses highlight strong binding affinities of quercetin for Y2080D and AZD0156 for C2770G, suggesting potential therapeutic options. In summary, this computational analysis provides a comprehensive understanding of ATM mutations, revealing their potential implications in cellular integrity and cancer development. The study underscores the significance of Y2080D and C2770G mutations, offering valuable insights for future precision medicine targeting-specific ATM. Despite informative computational analyses, a significant research gap exists, necessitating essential in vitro and in vivo studies to validate the predicted effects of ATM mutations on protein structure and function.

Antioxidant and Antidiabetic Potential of Ormocarpum cochinchinense (Lour.) Merr. Leaf: An Integrated In vitro and In silico Approach.

Diabetes is a prevalent metabolic disorder associated with various complications. Inhibition of α-glucosidase and α-amylase enzymes is an effective strategy for managing non-insulin-dependent diabetes mellitus. This study aimed to investigate the antioxidant and antidiabetic potential of Ormocarpum cochinchinense leaf through in vitro and in silico approaches. The methanol extract exhibited the highest phenolic and flavonoid content over solvent extracts aqueous, acetone, hexane, and chloroform, the same has been correlating with strong antioxidant activity. Furthermore, the methanol extract demonstrated significant inhibitory effects on α-amylase and α-glucosidase enzymes, indicating its potential as an antidiabetic agent. Molecular docking analysis identified compounds, including myo-inositol, with favorable binding energies comparable to the standard drug metformin. The selected compounds displayed strong binding affinity towards α-amylase and α-glucosidase enzymes. Structural dynamics analysis revealed that myo-inositol formed a more stable complex with the enzymes. These findings suggest that O. cochinchinense leaf possesses antioxidant and antidiabetic properties, making it a potential source for developing therapeutic agents.

Computational insights into NIMA-related kinase 6: unraveling mutational effects on structure and function.

The NEK6 (NIMA-related kinase 6) serine/threonine kinase is a pivotal player in a multitude of cellular processes, including the regulation of the cell cycle and the response to DNA damage. Its significance extends to disease pathogenesis, as changes in NEK6 activity have been linked to the development of cancer. Non-synonymous single nucleotide polymorphisms (nsSNPs) in NEK6 have been linked to cancer as they alter the protein's native structure and function. The association between NEK6 activity and cancer development has prompted researchers to explore the effects of genetic variations within the NEK6 gene. Therefore, we utilized advanced computational tools to analyze 155 high-confidence nsSNPs in the NEK6 gene. From this analysis, 21 nsSNPs were identified as potentially harmful, raising concerns about their impact on NEK6 activity and cancer risk. These 21 mutations were then examined for structural alterations, and eight of nsSNPs (I51M, V76A, I134N, Y152D, R171Q, V186G, L237R, and C285S) were found to destabilize the protein. Among the destabilizing mutations screened, a specific mutation, R171Q, stood out due to its conserved nature. To understand its impact on the protein and conformation, all-atom molecular dynamics simulations (MDS) for 100 ns were performed for both Wildtype NEK6 (WT-NEK6) and R171Q. The simulations revealed that the R171Q variant was unstable and led to significant conformational changes in NEK6. This study provides valuable insights into NEK6 dysfunction caused by single amino acid alterations, offering a novel understanding of the molecular mechanisms underlying NEK6-related cancer progression.

Andrographis paniculata (Burm.f.) Nees Alleviates Methotrexate-Induced Hepatotoxicity in Wistar Albino Rats.

Andrographis paniculata is a herbal plant used in traditional medicinal approaches to treat various ailments and diseases. Methotrexate (MTX) is a clinically used immunosuppressant and anticancer drug. One of the increasing concerns with MTX use is liver toxicity. The aim of this study is to investigate the potential effect of aqueous leaf extract of Andrographis paniculata against methotrexate-induced hepatotoxicity. Wistar albino rats were grouped into five groups, and the drugs were administered. MTX (20 mg/kg b.w.) was intraperitoneally injected into rats on the ninth day alone. Aqueous leaf extract of Andrographis paniculata (500 mg/kg b.w./day) was orally administered for 10 days. We confirmed the beneficial effect of aqueous extracts of Andrographis paniculata on restoring the hepatic enzyme markers, lipid profile, antioxidant level, anti-inflammatory marker (IL-10), anti-apoptosis (bcl-2), significant suppression of inflammatory cytokines (TNF-α, and IL-6), apoptosis marker (caspase 3) and cellular tissue damage caused by MTX. Overall, we revealed that Andrographis paniculata reduces critical aspects of oxidative stress, inflammatory processes, and apoptosis, thus protecting against methotrexate-induced hepatotoxicity.

Caesalpinia bonducella Counteracts Paracetamol-Instigated Hepatic Toxicity via Modulating TNF-α and IL-6/10 Expression and Bcl-2 and Caspase-8/3 Signalling.

Paracetamol is the most predominantly used antipyretic and analgesic drug. As paracetamol is metabolised mostly in the liver, both deliberate and unintentional overdoses of paracetamol are reported to provoke severe hepatotoxicity, including liver failure. Caesalpinia bonducella seed is well known for its medicinal and therapeutic properties. However, there is no report on its potential protective effects against paracetamol-instigated hepatotoxicity. Therefore, we studied the protective effects of aqueous seed extract of Caesalpinia bonducella (ASECB) on paracetamol-instigated hepatotoxicity in rats. Thirty female albino rats were divided into five groups: control, paracetamol-intoxicated, ASECB + paracetamol, silymarin + paracetamol, and ASECB alone. The rats were assessed for liver enzyme markers (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase), antioxidant activity (superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase), lipid peroxidation (malondialdehyde), histopathological, cytokine levels (pro-inflammatory cytokines TNF-α and IL-6, and anti-inflammatory cytokine IL-10), and protein expression (pro-apoptotic markers caspase 3 and caspase 8 and anti-apoptotic marker Bcl-2) after the 8-day study period. Repercussions of paracetamol intoxication induced upregulation of liver enzyme markers, antioxidant depletion, malondialdehyde production, decreased expression of Bcl-2 and IL-10, and overexpression of apoptotic and pro-inflammatory mediators, which were attenuated by pre-treatment with ASECB. ASECB markedly mitigated paracetamol-instigated liver injury by suppressing caspase-8/3 signalling and inflammatory infiltration in liver tissue by significantly reducing TNF-α and IL-6. In conclusion, ASECB pre-treatment exerts potent liver protection against paracetamol-instigated hepatotoxicity evidenced by mitigation of oxidative stress, lipid peroxidation, inflammation, and apoptosis.

Non-steroidal anti-inflammatory drugs (NSAIDs): A current insight into its molecular mechanism eliciting organ toxicities.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications that are routinely been used across the world. Their analgesic, anti-inflammatory, and antipyretic effects have all been well-documented. Moreover, they are been deliberated to have a protective role against various critical diseases such as cancer and cardiovascular diseases. However, the data presented by numerous studies in past have signified the adverse effects of NSAIDs due to overdosing on various systems such as cardiovascular, gastrointestinal, hepatic, renal, neural, etc. Despite substantial studies representing the mechanism behind the clinical risk of NSAIDs, there are very few reviews that have collated comprehensive records of various toxicities caused by overdosing on NSAIDs. As a result, we have presented a comprehensive overview of existing information on NSAIDs in this review. In addition to that, we have concentrated on presenting our understanding of various organ-based toxicities caused due to NSAID's prolonged use/overdosage.

NIMA-related kinase-6 (NEK6) as an executable target in cancer.

Cancer is a disease that develops when cells begin to divide uncontrollably and spreads to other parts of the body. Proliferation and invasion of cancerous cells are generally known to be influenced by cell cycle-related proteins in human malignancies. Therefore, in this review, we have emphasized on the serine/threonine kinase named NEK6. NEK6 is been deliberated to play a critical role in mitosis progression that includes mitotic spindle formation, metaphase to anaphase transition, and centrosome separation. Moreover, it has a mechanistic role in DNA repair and can cause apoptosis when inhibited. Past studies have connected NEK6 protein expression to cancer cell senescence. Besides, there are reports relating NEK6 to a range of malignancies including breast, lung, ovarian, prostate, kidney, liver, and others. Given its significance, this review attempts to describe the structural and functional aspects of NEK6 in various cellular processes, as well as how it is linked to different forms of cancer. Lastly, we have accentuated, on some of the plausible inhibitors that have been explored against NEK6 overexpression.

Exploring the Regulatory Role of ncRNA in NAFLD: A Particular Focus on PPARs.

Liver diseases are responsible for global mortality and morbidity and are a significant cause of death worldwide. Consequently, the advancement of new liver disease targets is of great interest. Non-coding RNA (ncRNA), such as microRNA (miRNA) and long ncRNA (lncRNA), has been proven to play a significant role in the pathogenesis of virtually all acute and chronic liver disorders. Recent studies demonstrated the medical applications of miRNA in various phases of hepatic pathology. PPARs play a major role in regulating many signaling pathways involved in various metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, encompassing a spectrum spanning from mild steatosis to severe non-alcoholic steatohepatitis (NASH). PPARs were found to be one of the major regulators in the progression of NAFLD. There is no recognized treatment for NAFLD, even though numerous clinical trials are now underway. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC), and its frequency increases as obesity and diabetes become more prevalent. Reprogramming anti-diabetic and anti-obesity drugs is an effective therapy option for NAFLD and NASH. Several studies have also focused on the role of ncRNAs in the pathophysiology of NAFLD. The regulatory effects of these ncRNAs make them a primary target for treatments and as early biomarkers. In this study, the main focus will be to understand the regulation of PPARs through ncRNAs and their role in NAFLD.

Immunomodulatory Role of Thioredoxin Interacting Protein in Cancer's Impediments: Current Understanding and Therapeutic Implications.

Cancer, which killed ten million people in 2020, is expected to become the world's leading health problem and financial burden. Despite the development of effective therapeutic approaches, cancer-related deaths have increased by 25.4% in the last ten years. Current therapies promote apoptosis and oxidative stress DNA damage and inhibit inflammatory mediators and angiogenesis from providing temporary relief. Thioredoxin-binding protein (TXNIP) causes oxidative stress by inhibiting the function of the thioredoxin system. It is an important regulator of many redox-related signal transduction pathways in cells. In cancer cells, it functions as a tumor suppressor protein that inhibits cell proliferation. In addition, TXNIP levels in hemocytes increased after immune stimulation, suggesting that TXNIP plays an important role in immunity. Several studies have provided experimental evidence for the immune modulatory role of TXNIP in cancer impediments. TXNIP also has the potential to act against immune cells in cancer by mediating the JAK-STAT, MAPK, and PI3K/Akt pathways. To date, therapies targeting TXNIP in cancer are still under investigation. This review highlights the role of TXNIP in preventing cancer, as well as recent reports describing its functions in various immune cells, signaling pathways, and promoting action against cancer.

Trichopus zeylanicus ameliorates ibuprofen inebriated hepatotoxicity and enteropathy: an insight into its modulatory impact on pro/anti-inflammatory cytokines and apoptotic signaling pathways.

Ibuprofen is a nonsteroidal anti-inflammatory drug that is commonly used for its analgesic, antipyretic and anti-inflammatory effects worldwide. However ibuprofen comes with serious unavoidable adverse effects on various organs when used for long duration or overdosed. Trichopus zeylanicus is a medicinal plant endemic to India owning various beneficial properties and is been used in treating various ailments. Therefore, the objective of this study was to evaluate the ameliorative effect of aqueous leaves' extract of Trichopus zeylanicus against ibuprofen-induced hepatic toxicity and enteropathy in rats. Overall in this study 30 male albino rats were used, which were divided into five groups (six in each group). Group-I was normal control, Group-II was ibuprofen (400 mg/kg/day) inebriated group, Group-III  was silymarin (25 mg/kg/day) pretreated  + ibuprofen (400 mg/kg/day), Group-IV was  ALETZ (1000 mg/kg/day) pretreated + ibuprofen (400 mg/kg/day), and Group-V was ALETZ alone (1000 mg/kg/day) group. The duration of the administration was for five days, followed by scarifying rats on the sixth day. Later the rats were assessed for liver and intestine enzyme markers, antioxidant parameters along with histopathological changes. In addition the pro-inflammatory markers such as TNF-α, IL-6 and IL-1ß as well as anti-inflammatory cytokine IL-10 levels were measured using ELISA. Lastly the expression pattern of apoptotic signaling markers such as caspase-3, caspase-8 and Bcl-2 was evaluated using western blot. The results obtained from this study showed changes in levels of aforesaid parameter which presented the toxic effect of ibuprofen on liver and small intestine. Pre-treatment of ALETZ in ibuprofen-inebriated group was able to normalize the adverse effect caused due to ibuprofen. The conclusion of the study deduces that pre-treatment with ALETZ alleviates by modulating oxidative stress, inflammation, and apoptosis in ibuprofen inebriated rats, indicating its protective mechanism.

Effect of baricitinib in regulating programmed death 1 and ligand programmed cell death ligand 1 through JAK/STAT pathway in psoriasis.

OBJECTIVES: Psoriasis is a chronic infectious skin disease triggered by an autoimmune process involving T-cell-mediated hyper-proliferation of keratinocytes. The objective of this study is to assess the modulation of programmed death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) through JAK/STAT pathway during the development of a psoriasis-like disease by both in vitro and in vivo model. Baricitinib, a known inhibitor of JAK1 and JAK2, was used to study the impact on PD-1 and PD-L1. MATERIALS AND METHODS: Human peripheral blood mononuclear cells (PBMC) were stimulated with either anti-CD3/CD28 or PMA/Ionomycin, to modulate level of PD-1 and PD-L1 under psoriasis-like condition. Interferon-gamma (IFNγ) was used to treat HaCaT cells to mimic the diseased keratinocytes found in Psoriatic patients. Psoriasis was induced with Imiquimod (IMQ) in animal model to study the cross-talk between different cell types and pathways. RESULTS: Expression levels of PD-1 and PD-L1 in PBMC, and secretion of cytokines, namely tumor necrosis factor-α (TNFα), IFNγ, interleukin (IL)-6, and IL-1 ß, were down-regulated on treatment with baricitinib. Further, in IFNγ-treated HaCaT cells (keratinocytes) mRNA levels of KRT-17 and PD-L1 were up-regulated.). Interestingly, in IFNγ-treated HaCat cells baricitinib decreased the levels of inflammatory cytokines such as IL-1 ß, IL-6, and TNFα along with KRT-17 and PD-L1. On IFNγ-treatment. Data from both PBMC and HaCaT suggest an anti-inflammatory role for this compound. Accordingly, baricitinib was able to alleviate disease symptom in IMQ induce mice model of psoriasis. As a consequence of baricitinib treatment down-regulation of p-STAT3, PD- and PD-L1 expression levels were observed. CONCLUSION: This study demonstrates a crosstalk between JAK/STAT and PD-1/PD-L1 pathways. It also demonstrates that cytokines such as IFNγ and IL-17 are down-regulated by baricitinib. We believe decreased expressions of PD-1 and PD-L1 may be a consequence of baricitinib-induced down-regulation of IFNγ and IL-17. More importantly, our data from the acute model of psoriasis indicates that PD-L1 behaves as a T-cell-associated T-cell-associated surrogate activation marker rather than immunosuppressive marker in early phase of psoriasis. Therefore it does not exhibit a causal relationship to disease.

Supplementation with β-carotene aids minimize inflammation in monosodium urate crystal- induced gouty arthritis in Wistar albino rats

Abstract Gout is a form of metabolic arthritis originated on grounds of increased accumulation of monosodium urate (MSU) crystals in joints. Current study focuses on anti-arthritic activities of β-carotene on MSU crystal-induced gouty arthritis rats in comparison with the non-steroidal anti-inflammatory drug, indomethacin. The evaluation was done by taking into account paw oedema, lysosomal enzymes, anti-oxidant enzymes, lipid peroxidation, serum biochemical parameters (uric acid, creatinine), serum cytokines (TNF-α, IL-1β) and histopathological studies. After the induction of MSU crystals, the lysosomal enzymes were increased, antioxidant enzymes were reduced, lipid peroxidation increased and paw volume increased. β-carotene treated at a dose of 10 mg/kg of body weight stabilizes lysosomal enzymes, increases anti-oxidant enzymes, regulates lipid peroxidation and decreased paw volume. The drug β-carotene potentially influences anti-inflammatory effects in arthritic group which is evident from the reduction in the elevated levels of inflammatory cytokines, TNF-α and IL-1β. Current study is an evidence of anti-inflammatory and anti-oxidant effects of β-carotene against MSU-crystal induced gouty arthritis rats.

Protective effect of the ethanolic and methanolic leaf extracts of Madhuca longifolia against diclofenac-induced toxicity in female Wistar albino rats.

BACKGROUND: Diclofenac is commonly prescribed Non-Steroidal Anti-Inflammatory Drug (NSAIDs) as it has anti-inflammatory, analgesic and anti-pyretic properties. Long term usage and over-dosage of diclofenac is associated with adverse effects like drug-induced liver injury, gastrointestinal and renal toxicity. The therapeutic uses of medicinal plants have gained a prominent role in recent years. Madhuca longifolia is a tree found throughout India, which is known to have several pharmacological activities. The aim of our study is to investigate the potential effect of the ethanolic and methanolic leaf extracts of M. longifolia against diclofenac-induced toxicity. METHODS: The rats used for the experiment were divided into seven groups. Group-1 was the normal control. Group-2 was administered with diclofenac (50 mg/kg b.w./day/ip) on the 4th and the 5th day. Group-3 was treated with diclofenac and ELEML (500 mg/kg b.w./day/po) on all 5 days. Group-4 was treated with diclofenac and MLEML (500 mg/kg b.w./day/po) on all 5 days. Standard drug silymarin (25 mg/kg b.w./day/po) was given to the rats of group-5 along with diclofenac. Group-6 and group-7 were treated with ethanolic leaf extract and methanolic leaf extract of M. longifolia respectively. After the study period, the rats were evaluated for parameters like liver and renal markers, antioxidants and histopathological changes. RESULTS: This study has proved the beneficial effect of ethanolic and methanolic leaf extract of M. longifolia against diclofenac-induced toxicity wherein ethanolic leaf extract showed a better result than methanolic leaf extract. CONCLUSION: Our study has concluded the beneficial effect of ethanolic and methonolic leaf extract of Madhuca longifolia against DFC-induced toxicity. This study proves that it has potential effect on hepato, renal and gastro toxicity in female Wistar albino rats. It can further be studied to understand its mechanism in treating toxicity.

Characterization of ex vivo cultured limbal, conjunctival, and oral mucosal cells: A comparative study with implications in transplantation medicine.

PURPOSE: Limbal epithelial stem cell deficiency is caused by exposure of the cornea to thermal, chemical, or radiation burns or by diseases (aniridia and Stevens-Johnson syndrome). Autologous cell transplantation is a widely used therapeutic modality for restoring the corneal surface in such pathological conditions. Ex vivo cultured limbal, conjunctival, and oral biopsies have been widely used to reconstruct the corneal surface with variable outcomes. Culture characterization of the ex vivo cultured cells would provide insight and clues into the underlying signaling mechanisms that would aid in determining the probable transplantation outcome. Comparison of the vital proteins and genes among the three ex vivo cultured tissues has implications in clinical practice. To address this issue, we characterized and compared the proliferative and differentiated properties of ex vivo cultured limbal, conjunctival, and oral biopsies used for cell-based therapy for corneal surface restoration. METHODS: Limbal, conjunctival, and oral biopsies were collected with informed patient consent. Explant cultures were established on the denuded human amniotic membrane with corneal lineage differentiation medium. The day 14 cultures were characterized for epithelial and corneal lineage-specific markers using reverse transcription (RT)-PCR for cytokeratin 3, 4, 12, 13, 15, connexin 43, vimentin, p63α, and ABCG2 markers. mRNA expression was estimated in day 14 cultures with real-time quantitative real time (qRT)-PCR for pluripotency markers (OCT4, SOX2, NANOG), putative corneal stem cell markers (ABCG2 and p63α), proliferation markers (cyclin d1, Ki-67, PCNA, and CDC20), apoptotic markers (BCL2, BAX, caspase 3, and caspase 9), Notch signaling pathway markers (Notch1, Jagged1, Hes1, Hes3, Hes5, and Hey1), and autophagic markers (LC3A, LC3B, ATG7, RAB7, LAMP1, and LAMP2). Fluorescence-activated cell sorter profiling was performed for pluripotent markers and putative corneal stem cell markers ABCG2 and p63α. RESULTS: The protein and mRNA expression levels of the pluripotent markers were lower, whereas those of the putative stem/progenitor markers ABCG2, ΔNp63α, and Notch signaling molecules (Notch1 and Jagged1) were elevated in limbal cultures. The gene expression levels of the autophagy markers (LC3A, LC3B, and LAMP1) were significantly increased in the limbal cultures compared to the oral and conjunctival cultures. CONCLUSIONS: In conclusion, the limbal epithelial cultures showed higher expression of proliferative, limbal stem cell marker, Notch signaling, and autophagy markers suggesting a role in stem cell maintenance and differentiation. This implicates the probable factors that might drive a successful transplantation. Our findings provide the initial steps toward understanding transplantation medicine in an ex vivo model.

Protective role of Triphala, an Indian traditional herbal formulation, against the nephrotoxic effects of bromobenzene in Wistar albino rats.

OBJECTIVE: The purpose of the present study was to evaluate the nephroprotective and antioxidant properties of Triphala against bromobenzene-induced nephrotoxicity in female Wistar albino rats. METHODS: Animals were divided into five groups of six rats and treated as follows: Group I was a normal control and received no treatment, Group II received only bromobenzene (10 mmol/kg), Groups III and IV received bromobenzene and Triphala (250 and 500 mg/kg, respectively), Group V received Triphala alone (500 mg/kg), and Group VI received bromobenzene and silymarin (100 mg/kg). Antioxidant status and serum kidney functional markers were analyzed. RESULTS: Bromobenzene treatment resulted in significant (P< 0.05) decreases in the activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase as well as total reduced glutathione. There was a significant (P< 0.05) increase in lipid peroxidation in kidney tissue homogenates. There were significant (P< 0.05) reductions in the levels of serum total protein and albumin as well as significant (P< 0.05) increases in serum creatinine, urea and uric acid. The oral administration of two different doses (250 and 500 mg/kg) of Triphala in bromobenzene-treated rats normalized the tested parameters. The histopathological examinations of kidney sections of the experimental rats support the biochemical observations. CONCLUSION: Triphala treatment alleviated the nephrotoxic effects of bromobenzene by increasing the activities of antioxidant enzymes and reducing the levels of lipid peroxidation and kidney functional markers.