Astaxanthin as an Anticancer Agent against Breast Cancer: An In Vivo and In Vitro Investigation.

AIM: This study aimed to investigate the antioxidant properties, cytotoxic activity, and apoptotic effects of astaxanthin (ASX) on genes and pathways involved in breast cancer in Balb/c mice models injected with the 4T1 cell line. BACKGROUND: ASX could inhibit some tumor progression by using in vivo and in vitro models. OBJECTIVE: The effect of ASX on breast cancer was not fully understood till now. METHOD: In an in vivo model, 4T1 cells-injected mice were administered with different concentrations of ASX (100 and 200 mg/kg), and histopathological evaluations were done using an optical microscope and the hematoxylin and eosin (H&E) staining. The real- time PCR investigated the expression levels of B-cell lymphoma 2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and Caspase 3 genes in mice treated with 100 and 200 mg/kg ASX. Also, the level of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined in ASX-treated cancer mice. RESULTS: ASX (200 mg/kg) caused a significant reduction in the mitotic cell count of tumor tissues compared to ASX (100 mg/kg). The antiproliferative effects of different concentrations of ASX were shown based on the MTT results. The treatment of breast tumor mice with both concentrations of ASX, especially 200 mg/kg, elevated the expression of Caspase 3, Bax, and SOD enzyme levels and decreased Bcl-2 expression and MDA enzyme levels. CONCLUSION: ASX can be considered a promising alternative treatment for breast cancer.

Protective Effects of Curcumin and Nanomicelle Curcumin on Chlorpyrifos-induced Oxidative Damage and Inflammation in the Uterus, Ovary and Brain of Rats.

BACKGROUND AND AIMS: Chlorpyrifos (CPF), which is classified as an Organophosphorus Pesticide (OP), has been identified as a toxic agent for the reproductive system due to its capacity to induce oxidative stress and inflammation. Curcumin (CUR) has been reported as a natural antioxidant and anti-inflammatory agent that could combat toxicity in various tissues. This study aims to examine the protective effects of CUR and its nanoformulation against reproductive impairment induced by CPF. METHOD: Forty-eight female Wistar albino rats were randomly allocated to six groups (n=8): control (0.5 mL of corn oil, the solvent for CPF), CPF (10 mg/kg), CPF + CUR 100 mg/kg/day, CPF + CUR 300 mg/kg/day, CPF + nano-micelle curcumin (NMC) 2.5 mg/kg/day, and CPF + NMC 5 mg/kg/day. The experimental treatment was performed for 30 days. Then, brain, ovary and uterus tissues were collected for measuring oxidative stress and inflammatory indices. RESULT: MDA, NO, IL-6, and TNF-α concentrations significantly increased in the brain, ovary and uterus of the CPF group versus the control group (p < 0.001). The levels of GSH and SOD in the uterus, ovaries, and brain exhibited a significant decrease in the CPF group compared to the control group (p < 0.05). However, CUR (300 mg/kg) and NMC (5 mg/kg) significantly decreased MDA, NO, TNF-α, and Il-6 and increased SOD and GSH levels in the uterus, ovaries and brain of the CPF-exposed animals versus the CPF-exposed non-treated animals (p < 0.001). CONCLUSION: Our findings indicated that CUR and NMC could be effective in alleviating CPFinduced reproductive toxicity.

Corrigendum to "Oxidative stress and apoptotic index modifications in the hippocampus of rat pups born to mothers exposed to buprenorphine during lactation" [Toxicol. Rep. 2022 Nov 19; 9: 2050-2054. doi: 10.1016/j.toxrep.2022.11.005. PMID: 36518388; PMCID: PMC9742962].

[This corrects the article DOI: 10.1016/j.toxrep.2022.11.005.].

Nrf2 Mediates Effect of Resveratrol in Ischemia-reperfusion Injury.

Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and intracellular pH, reducing oxidative reactions, increasing lactic acid release, and activating anaerobic metabolism. Reperfusion restores aerobic respiration and increases ROS production, leading to malfunction of transmembrane transport, activation of proteases, DNA dissolution, and protein denaturation, leading to apoptotic cell death. Nrf2 is a transcription factor that regulates cellular inflammation and oxidative responses. It is activated by oxidants and electrophiles and enhances detoxifying enzyme expression, maintaining redox homeostasis. It also activates ARE, which activates several ARE-regulated genes that favor cell survival by exhibiting resistance to oxidants and electrophiles. Nrf2 regulates the antioxidant defense system by producing phase II and antioxidant defense enzymes, including HO-1, NQO-1, gglutamylcysteine synthetase, and rate-limiting enzymes for glutathione synthesis. Nrf2 protects mitochondria from damage and supports mitochondrial function in stress conditions. Resveratrol is a stilbene-based compound with a wide variety of health benefits for humans, including antioxidant, anticarcinogenic, antitumor, and estrogenic/antiestrogenic. Resveratrol protects against IRI through several signaling pathways, including the Nrf2/ARE pathway. Here, we review the studies that investigated the mechanisms of resveratrol protection against IRI through modulation of the Nrf2 signaling pathway.

Neuroprotective Effects of Curcumin against Chronic ChlorpyrifosInduced Oxidative Damage in Rat Brain Tissue.

BACKGROUND: Chlorpyrifos (CPF) is an organophosphate pesticide that inhibits acetylcholinesterase (AChE) activity. Investigations have also focused on its neurotoxicity, which is independent of AChE inhibition. Here, we evaluated the effect of CPF on oxidative indices in the brain tissue and explored the protective effect of curcumin (Cur) against its toxicity. METHODS: Forty male Wistar rats were divided into five groups, each consisting of eight rats (n = 8) per group. Animals were administrated by oral gavage for 90 days with the following treatments: control (C), CPF, CPF + CUR 25 mg/kg, CPF + CUR50, and CPF + cur 100 received olive oil, CPF, CPF plus 25 mg/kg of CUR, CPF plus 50 mg/kg of CUR, and CPF plus 100 mg/kg of CUR, respectively. After anesthetization, animal brain tissues were obtained for assessment of oxidative stress indices. RESULTS: The concentration of MDA significantly increased in the brains of the CPF group as compared to the control group (p < 0.01). Also, a significant decrease in MDA concentrations was observed in the brains of rats in the CPF + Cur 100 group compared to the CPF group (p < 0.05). A significant decrease was noted in the GSH concentration in the brains of the CPF group compared to the control group (p < 0.05). Treatment with Cur at 100 mg/kg exhibited a significant increase in GSH concentrations in the brains of the CPF-exposed group compared to the CPF group without Cur administration (p < 0.05). The concentration of NO exhibited a significant increase in the brains of the CPF group when compared to the control group (p < 0.05). Also, a significant decrease in NO concentration was observed in the brain tissue of the CPF + Cur 100 group compared to the CPF group (p < 0.05). CONCLUSION: Our data establish that chronic exposure to CPF induced oxidative stress in brain tissue, which was reversed by CUR administration. Additional experimental and clinical investigations are needed to validate the efficacy of CUR as a potential antidote for CPF poisoning.

A Review of the Dual Role of MicroRNA-21 in Cardiovascular Diseases: Risk Factor or a Potential Therapeutic Target.

Cardiovascular diseases [CVD] are the number one reason for morbidity and mortality in the modern world, and their incidence is increasing at an incredible pace. Increasing evidence has shown the significant functions of microRNAs in the cardiovascular system and has highlighted their potential application as a new era of diagnostic and therapeutic targets for CVD that can improve the prognosis and life expectancy of patients. Among more than 2,000 microRNAs, microRNA-21 [miR-21] is highly expressed in human hearts and has earned the interest of researchers as a potential biomarker in a wide range of common heart conditions. Here, we summarized recent research progress regarding the significant role of miR-21 in CVD, focusing on cardiotoxicity, heart arrhythmias, cardiomyopathies, and hypertension. Several signaling pathways [TGF-ß1/Smad2 signaling, FGFR1/FGF21/PPARγ, NF-κB/miR-21/SMAD7, miR-21/SPRY1/ERK/mTOR …] and molecular targets [BTG2, PDCD4, PTEN, STAT3…] were reported to be controlled, at least partially, by miR-21 and are linked to CVD pathogenesis. Most investigations highlighted miR-21 cardioprotective functions in heart injury, while some other studies showed that this miR is elevated in the serum/tissue of patients, promoting fibrosis and cardiac dysfunction. This dual role can be explained by the fact that miR-21 has multiple regulatory functions depending on the microenvironment, downstream signaling, and target genes, which indicates that cell-type-specific investigations should receive more attention. With further investigations, miR-21 can be considered a novel tailored therapy with favorable outcomes.

Therapeutic Effect of Resveratrol and its Novel Formulations on Lung Cancer: Focus on Biological Aspects and Underlying Pathways.

Lung cancer is a leading cause of mortality and morbidity worldwide. Due to significant advances in therapeutic strategies, patients' survival and life quality have been improved, however there is still an urgent requirement for developing more effective therapeutic methods. Resveratrol, a natural polyphenol with numerous biological potentials, has been widely studied. It has shown therapeutic potetial in various diseases including neurodegenerative diseases, cardiovascular disorders, and cancers through the regulation of key cellular signaling such as apoptosis, as well as molecular pathways such as microRNA modulation. It has been reported that resveratrol acts as an anticancer agent against lung cancer in vivo and in vitro. Resveratrol could combat against lung cancer by modulating various molecular targets and signaling pathways involved in oxidative stress, inflammation, apoptosis and autoghagy and also microRNAs expression. Moreover, novel delivery systems and analogs have recently been introduced to promote the anticancer impacts of resveratrol. In this article, we review current evidence on the anticancer effects of resveratrol and its novel formulations in the treatment of lung cancer with a focus on underlying mechanisms.

Carbamate compounds induced toxic effects by affecting Nrf2 signaling pathways.

Carbamate (CBs) is a class of insecticides which is being known as an important cause of intentional or accidental poisoning. CBs, cause carbamylation of acetylcholinesterase at neuronal synapses and neuromuscular junction. Exposure to CBs through skin contact, inhalation, or ingestion can result in significant cholinergic toxicity. This is due to the elevation of acetylcholine levels at ganglionic synapses found in both the sympathetic and parasympathetic nervous systems, as well as muscarinic receptors located in target organs of the parasympathetic nervous system, nicotinic receptors situated in skeletal muscle tissue, and the central nervous system. The association between human illnesses and environmental exposures to CBs have been extensively studied in several studies. Although CBs-triggered toxicity leads to overproduction of reactive oxygen species (ROS), the detailed association between the toxicity under CBs exposure and NFE2-related factor 2 (Nrf2) signaling pathways has not been completely clarified. In this review we aimed to summarize the latest findings on the functional interrelationship between carbamates compounds and Nrf2 signaling.

Anticancer Properties of Baicalin against Breast Cancer and other Gynecological Cancers: Therapeutic Opportunities based on Underlying Mechanisms.

Gynecological cancers are serious life-threatening diseases responsible for high morbidity and mortality around the world. Chemotherapy, radiotherapy, and surgery are considered standard therapeutic modalities for these cancers. Since the mentioned treatments have undesirable side effects and are not effective enough, further attempts are required to explore potent complementary and/or alternative treatments. This study was designed to review and discuss the anticancer potentials of baicalin against gynecological cancers based on causal mechanisms and underlying pathways. Traditional medicine has been used for thousands of years in the therapy of diverse human diseases. The therapeutic effects of natural compounds like baicalin have been widely investigated in cancer therapy. Baicalin was effective against gynecological cancers by regulating key cellular mechanisms, including apoptosis, autophagy, and angiogenesis. Baicalin exerted its anticancer property by regulating most molecular signaling pathways, including PI3K/Akt/mTOR, NFκB, MAPK/ERK, and Wnt/ß-catenin. However, more numerous experimental and clinical studies should be designed to find the efficacy of baicalin and the related mechanisms of action.

Application of Quercetin and its Novel Formulations in the Treatment of Malignancies of Central Nervous System: An Updated Review of Current Evidence Based on Molecular Mechanisms.

Quercetin, a naturally occurring polyphenolic compound found in abundance in vegetables and fruits, has emerged as a compelling subject of study in cancer treatment. This comprehensive review delves into the significance and originality of quercetin's multifaceted mechanisms of action, with a particular focus on its application in various brain tumors such as glioblastoma, glioma, neuroblastoma, astrocytoma, and medulloblastoma. This review scrutinizes the distinctive facets of quercetin's anti-cancer properties, highlighting its capacity to modulate intricate signaling pathways, trigger apoptosis, impede cell migration, and enhance radiosensitivity in brain tumor cells. Significantly, it synthesizes recent research findings, providing insights into potential structure-activity relationships that hold promise for developing novel quercetin derivatives with heightened effectiveness. By unraveling the unique attributes of quercetin's anti-brain tumor effects and exploring its untapped potential in combination therapies, this review contributes to a deeper comprehension of quercetin's role as a prospective candidate for advancing innovative treatments for brain cancer.

Therapeutic Effects of Berberine against Urological Cancers: Biological Potentials Based on Cellular Mechanisms.

Urological cancers, including prostate, kidney, and bladder cancer are problematic human diseases worldwide. Current strategies for the treatment of these cancers are chemotherapy, radiotherapy, surgery, or a combination of mentioned therapies. Due to the high mortality and morbidity rate of urological cancers and possible side effects of available standard treatments, searching for more effective and safe treatments is a critical issue. The beneficial properties of natural compounds, such as berberine, have been widely investigated in human diseases. Moreover, the anticancer potential of this agent has been extensively documented, especially in experimental studies. In this review, we have tried to discuss the effect of berberine against urological cancers, focusing on cellular and molecular mechanisms.

Protective Roles and Therapeutic Effects of Gallic Acid in the Treatment of Cardiovascular Diseases: Current Trends and Future Directions.

Cardiovascular diseases (CVDs) are serious life-threatening illnesses and significant problematic issues for public health having a heavy economic burden on all society worldwide. The high incidence of these diseases as well as high mortality rates make them the leading causes of death and disability. Therefore, finding novel and more effective therapeutic methods is urgently required. Gallic acid, an herbal medicine with numerous biological properties, has been utilized in the treatment of various diseases for thousands of years. It has been demonstrated that gallic acid possesses pharmacological potential in regulating several molecular and cellular processes such as apoptosis and autophagy. Moreover, gallic acid has been investigated in the treatment of CVDs both in vivo and in vitro. Herein, we aimed to review the available evidence on the therapeutic application of gallic acid for CVDs including myocardial ischemia-reperfusion injury and infarction, drug-induced cardiotoxicity, hypertension, cardiac fibrosis, and heart failure, with a focus on underlying mechanisms.

Targeting the NF-E2-related factor 2 pathway for overcoming leukemia.

Leukemia is cancer of the body's blood-forming tissues, including the bone marrow and the lymphatic system. There are many types of leukemia that some of them occur in children and the others are more common in adults. Currently, there are many different chemotherapy agents for leukemia while chemoresistance increases the survival of the leukemic cells. One of the main reasons of chemoresistance, is a transcription factor called Nuclear factor erythroid 2-Related Factor 2 (NRF2). An increase in NRF2 expression in leukemic cells which are being treated with chemotherapy agents, can increase the survival of these cells in the presence of therapeutics. Accordingly, the inhibition of NRF2 by different methods as a cotreatment with classical chemotherapy agents, can be a promising procedure in leukemia treatment. In this study we focus on the association of NRF2 and leukemia and targeting it as a new therapeutic method in leukemia treatment.

The Protective Effect of Curcumin Against Cardiotoxic Effects Induced by Chronic Exposure to Chlorpyrifos.

AIMS: This study aimed to evaluate the effect of Chlorpyrifos (CPF) in rat heart tissue and the effect of Curcumin (Cur) on cardiac enzymes, oxidative indices, and histopathological changes in the cardiac tissue. BACKGROUND: CPF, the most used organophosphorus pesticide (OP), has been reported to induce cardiotoxic effects. OBJECTIVE: The cardioprotective effects of Cur against CPF-induced toxicity have not been entirely investigated till now. METHOD: Forty male Wistar rats were randomized into five groups (n=8). C group (Control animals that received olive oil), CPF group (10 mg/kg/day), CPF + Cur 25, CPF + Cur 50, and CPF + Cur 100 groups (animals received 10 mg/kg/day CPF and 25, 50, and 100 mg/kg Cur, respectively). All treatments were administered via oral gavage for 90 days. Cardiac enzymes (LDH & CPK) and oxidative stress (OS) biomarkers in heart tissue (malondialdehyde, Superoxide Dismutase) were measured. Histopathological changes in the heart tissue were also evaluated. RESULT: Chronic exposure to CPF significantly increased cardiac enzyme levels and OS biomarkers. Histological changes were found, including disorganization of the cardiac muscle fibers with disorganization and degeneration in myocardial fibers with separation of myofibrils and cytoplasmic vacuolization of cardiac muscle fibers. Administration of Cur (100 mg/kg) reversed serum LDH concentration and OS biomarkers to normal levels in CPF-exposed animals (p < 0.05) and significantly improved cardiac damage. CONCLUSION: According to the results of this study, Cur can reduce the adverse effects of long-term exposure to CPF in rat heart tissue by modulating OS.

miRNA contributes to neuropathic pains.

Neuropathic pain (NP) is a kind of chronic pain caused by direct injury to the peripheral or central nervous system (CNS). microRNAs (miRNAs) are small noncoding RNAs that mostly interact with the 3 untranslated region of messenger RNAs (mRNAs) to regulate the expression of multiple genes. NP is characterized by changes in the expression of receptors and mediators, and there is evidence that miRNAs may contribute to some of these alterations. In this review, we aimed to fully comprehend the connection between NP and miRNA; and also, to establish a link between neurology, biology, and dentistry. Studies have shown that targeting miRNAs may be an effective therapeutic strategy for the treatment of chronic pain and potential target for the prevention of NP.

Anticancer activity of thymoquinone against breast cancer cells: Mechanisms of action and delivery approaches.

The rising incidence of breast cancer has been a significant source of concern in the medical community. Regarding the adverse effects and consequences of current treatments, cancers' health, and socio-economical aspects have become more complicated, leaving research aimed at improved or new treatments on top priority. Medicinal herbs contain multitarget compounds that can control cancer development and advancement. Owing to Nigella Sativa's elements, it can treat many disorders. Thymoquinone (TQ) is a natural chemical derived from the black seeds of Nigella sativa Linn proved to have anti-cancer and anti-inflammatory properties. TQ interferes in a broad spectrum of tumorigenic procedures and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis owing to its multitargeting ability. It effectively facilitates miR-34a up-regulation, regulates the p53-dependent pathway, and suppresses Rac1 expression. TQ promotes apoptosis and controls the expression of pro- and anti-apoptotic genes. It has also been shown to diminish the phosphorylation of NF-B and IKK and decrease the metastasis and ERK1/2 and PI3K activity. We discuss TQ's cytotoxic effects for breast cancer treatment with a deep look at the relevant stimulatory or inhibitory signaling pathways. This review discusses the various forms of polymeric and non-polymeric nanocarriers (NC) and the encapsulation of TQ for increasing oral bioavailability and enhanced in vitro and in vivo efficacy of TQ-combined treatment with different chemotherapeutic agents against various breast cancer cell lines. This study can be useful to a broad scientific community, comprising pharmaceutical and biological scientists, as well as clinical investigators.

Anti-gout and urate-lowering potentials of curcumin: A review from bench to beside.

BACKGROUND: Gouty arthritis is a complex form of inflammatory arthritis, triggered by the sedimentation of monosodium urate crystals in periarticular tissues, synovial joints, and other sites in the body. Curcumin is a natural polyphenol compound, isolated from the rhizome of the plant Curcuma longa, possessing countless physiological features, including antioxidant, anti-inflammatory, and anti-rheumatic qualities. OBJECTIVE: This study aimed to discuss the beneficial impacts of curcumin and its mechanism in treating gout disease. METHODS: Ten English and Persian databases were used to conduct a thorough literature search. Studies examining the anti-gouty arthritis effects of curcumin and meeting the inclusion criteria were included. RESULTS: According to the studies, curcumin has shown xanthine oxidase and urate transporter-1 inhibitory properties, uric acid inhibitory characteristics, and antioxidant and anti-inflammatory effects. However, some articles found no prominent reduction in uric acid levels. CONCLUSION: In this review, we emphasized the potency of curcumin and its compounds against gouty arthritis. Despite the potency, we suggest an additional well-designed evaluation of curcumin, before its therapeutic effectiveness is completely approved as an anti-gouty arthritis agent.

Polychlorinated biphenyls and thyroid function: a scoping review.

OBJECTIVE: Numerous evidence indicates the association between polychlorinated biphenyls (PCBs), an endocrine disrupter, with thyroid hormone disruption, contradictory findings also exist. Herein, we tried to address this question by performing a scoping review. CONTENT: The search was performed on PubMed, Scopus, Web of Science, and Google Scholar databases from 2010 onwards. Animal studies on PCBs' effect on thyroid function were searched. The SYRCLE's RoB scale assessed the risk of bias. I2 and Q tests are used for investigating heterogeneity. A random-effects model with the pooled standard means difference (SMD) and 95 % confidence interval (CI) was performed for the TSH, TT4, TT3, and FT4 outcomes using Comprehensive Meta-Analyses (CMA) Software version 3. Also, we conducted subgroup analyses based on the different types of PCB. The initial search identified 1,279 publications from the main databases 26 of them fulfilled our eligibility criteria for the study, and then five studies among selected studies had sufficient data for analysis. Meta-analysis of data revealed that Aroclor 1260 (SDM: -0.47, 95 % CI: -0.92, -0.01, p=0.044) and PCB 126 (SDM: 0.17, 95 % CI: -0.40, 0.75, p=0.559) significantly increased TSH concentration in the exposed groups vs. the control groups. Related to the effects of PCBs on the TT4, our findings indicated a significant reduction the TT4 concentration of animals exposed to Aroclor 1260 (SDM: -5.62, 95 % CI: -8.30, -2.94, p=0.0001), PCB 118 (SDM: -6.24, 95 % CI: -7.76, -4.72, p=0.0001), PCB 126 (SDM: -1.81, 95 % CI: -2.90, -0.71, p=0.001), and PCB 153 (SDM: -1.32, 95 % CI: -2.29, -0.35, p=0.007) vs. the controls. Our meta-analysis indicated a significant increase in TT3 concentration following exposure to PCB 118 and PCB 153 (SDM: -0.89, 95 % CI: -1.36, -0.42, p=0.0001, and SDM: -1.45, 95 % CI: -2.15, -0.75, p=0.0001, respectively). Aroclor 1254 and PCB 126 significantly decreased TT3 concentration (SDM: 1.25, 95 % CI: 0.29, 2.21, p=0.01 and SDM: 3.33, 95 % CI: 2.49, 4.18, p=0.0001, respectively). PCB 126 significantly decreased FT4 in the exposed groups vs. the control groups (SDM: -7.80, 95 % CI: -11.51, -5.35, p=0.0001). SUMMARY: Our findings showed an association between PCBs exposure and hypothyroidism in rodents, fish, and chicken embryos. OUTLOOK: Regarding to the most evidence of hypothyroidism effects of PCBs in animal species, it is necessary to consider large cohort studies to address the association between PCBs exposure and thyroid function impairment in humans.

Oncogenic alterations of metabolism associated with resistance to chemotherapy.

Metabolic reprogramming in cancer cells is a strategy to meet high proliferation rates, invasion, and metastasis. Also, several researchers indicated that the cellular metabolism changed during the resistance to chemotherapy. Since glycolytic enzymes play a prominent role in these alterations, the ability to reduce resistance to chemotherapy drugs is promising for cancer patients. Oscillating gene expression of these enzymes was involved in the proliferation, invasion, and metastasis of cancer cells. This review discussed the roles of some glycolytic enzymes associated with cancer progression and resistance to chemotherapy in the various cancer types.

Differences in clinical and lab characteristics of sepsis between opium user patients and patients with no illicit drug addiction.

BACKGROUND: Sepsis is a significant cause of mortality worldwide. This study aimed to compare clinical and laboratory characteristics of sepsis in patients addicted to illicit drugs versus patients with no illicit drug addiction. METHODS: In this cross-sectional study, all patients hospitalized with sepsis diagnosis were recruited within six months from September to March 2019. Sixty patients for each group (illicit drug-addicted and non-addicted individuals) were selected. The data relating to illicit drug consumption, serum indices, the current focus of infection, duration of hospitalization, and disease outcomes were collected. Patients who had an illicit drug addiction were compared with non-addicted patients in terms of clinical and laboratory parameters. The data collected were analyzed using SPSS software (version 19). RESULTS: The bacterial load in the urine culture was statistically significant in both groups and higher in the non-addicted group. The frequency distributions of focus of infection, duration of hospitalization, and outcome were not significantly different between the two groups. The serum sodium and total neutrophils were significantly higher in the addicted group. However, the MCHC level was significantly lower (p<0.05). CONCLUSION: Opium may have stimulated the immune system and reduced bacterial infection in septic patient users.