Anti-inflammatory, antioxidant and anti-mitophagy effects of trans sodium crocetinate on experimental autoimmune encephalomyelitis in BALB/C57 mice.

Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100 mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100 mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund's adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1ß and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100 mg/kg) administration on day 16. Furthermore, TSC (50 and 100 mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100 mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1ß and TNF-α. Notably, TSC (100 mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels. These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.

Evaluation of Anti-Nociceptive, Anti-Inflammatory, and Anti-Fibrotic effects of noscapine against a rat model of Achilles tendinopathy.

During tendinopathy, prolonged inflammation results in fibrosis and the adherence of tendons to the adjacent tissues, causing discomfort and movement disorders. As a natural compound, noscapine has several anti-inflammatory and anti-fibrotic properties. Therefore, we aimed to investigate the effects of noscapine against a rat model of tendinopathy. We created a surgical rat model of Achilles tendon damage to emulate tendinopathy. Briefly, an incision was made on the Achilles tendon, and it was then sutured using an absorbable surgical thread. Immediately, the injured area was topically treated with the vehicle, noscapine (0.2, 0.6, and 1.8 mg/kg), or dexamethasone (0.1 mg/kg) as a positive control. During the 19-day follow-up period, animals were assessed for weight, behavior, pain, and motor coordination testing. On day 20th, the rats were sacrificed, and the tendon tissue was isolated for macroscopic scoring, microscopic (H&E, Masson's trichrome, Ki67, p53) analyses, and cytokine secretion levels. The levels of macroscopic parameters, including thermal hyperalgesia, mechanical and cold allodynia, deterioration of motor coordination, tendon adhesion score, and microscopic indices, namely histological adhesion, vascular prominence and angiogenesis, and Ki67 and p53 levels, as well as fibrotic and inflammatory biomarkers (IL-6, TNF-α, TGF-ß, VEGF) were significantly increased in the vehicle group compared to the sham group (P < 0.05-0.001 for all cases). In contrast, the administration of noscapine (0.2, 0.6, and 1.8 mg/kg) attenuated the pain, fibrosis, and inflammatory indices in a dose-dependent manner compared to the vehicle group (P < 0.05-0.001). Histological research indicated that noscapine 0.6 and 1.8 mg/kg had the most remarkable healing effects. Interestingly, two higher doses of noscapine had impacts similar to those of the positive control group in both clinical and paraclinical assessments. Taken together, our findings suggested that noscapine could be a promising medicine for treating tendinopathies.

Melatonin attenuates liver injury in arsenic-treated rats: The potential role of the Nrf2/HO-1, apoptosis, and miR-34a/Sirt1/autophagy pathways.

Arsenic is a toxic metalloid found in the environment in different organic and inorganic forms. Molecular mechanisms implicated in arsenic hepatotoxicity are complex but include oxidative stress, apoptosis, and autophagy. The current study focused on the potential protective capacity of melatonin against arsenic-induced hepatotoxicity. Thirty-six male Wistar rats were allocated into control, arsenic (15 mg/kg; orally), arsenic (15 mg/kg) plus melatonin (10, 20, and 30 mg/kg; intraperitoneally), and melatonin alone (30 mg/kg) groups for 28 days. After the treatment period, the serum sample was separated to measure liver enzymes (AST and ALT). The liver tissue was removed and then histological alterations, oxidative stress markers, antioxidant capacity, the levels of Nrf2 and HO-1, apoptosis (Bcl-2, survivin, Mcl1, Bax, and caspase-3), and autophagy (Sirt1, Beclin-1, and LC3 II/I ratio) proteins, as well as the expression level of miR-34a, were evaluated on this tissue. Arsenic exposure resulted in the enhancement of serum AST, ALT, and substantial histological damage in the liver. Increased levels of malondialdehyde, a lipid peroxidation marker, and decreased levels of physiological antioxidants including glutathione, superoxide dismutase, and catalase were indicators of arsenic-induced oxidative damage. The levels of Nrf2, HO-1, and antiapoptotic proteins diminished, while proapoptotic and autophagy proteins were elevated in the arsenic group concomitant with a low level of hepatic miR-34a. The co-treatment of melatonin and arsenic reversed the changes caused by arsenic. These findings showed that melatonin reduced the hepatic damage induced by arsenic due to its antioxidant and antiapoptotic properties as well as its regulatory effect on the miR-34a/Sirt1/autophagy pathway.

The Hepatorenal Protective Potential of Caffeic Acid Consumption on the Arsenic-Exposed Syrian Mice.

Arsenic can induce lethal hepatorenal insufficiency by inducing progressive cytotoxicity in the two main body's hemostatic regulators, the kidney and liver. In the current study, the hepatorenal protective impact of caffeic acid was investigated in arsenic-exposed Syrian mice. Twenty-four male Syrian mice (30 ± 8 g) were provided and randomly divided into 4 groups of 6 receiving nothing, arsenic, arsenic and caffeic, and caffeic acid. The mice passed the 21-day treatment program. The mice's blood was collected and analyzed by measuring the serum ALT/AST enzymes and creatinine/urea levels, respectively. Finally, the histopathological properties in both the kidney and liver organs of the mice were studied. Arsenic administration significantly increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), LDH, urea, and creatinine concentrations (p < 0.05). Simultaneous administration of caffeic acid with arsenic decreased the serum AST and creatinine (p < 0.05). Moreover, the renal glomerulus and liver regeneration in the mice receiving caffeic acid supplements exhibited the caffeic acid hepatorenal protective potential. The histopathological changes caused by arsenic in the mice's liver and kidney tissue including degeneration, necrosis, hyperemia, and tissue hypotrophy were shifted to normal conditions following the caffeic acid administration dose, which was verified by the mice blood biochemical analysis results.

Melatonin Attenuates Arsenic-Induced Neurotoxicity in Rats Through the Regulation of miR-34a/miR-144 in Sirt1/Nrf2 Pathway.

Arsenic (As) exposure is known to cause several neurological disorders through various molecular mechanisms such as oxidative stress, apoptosis, and autophagy. In the current study, we assessed the effect of melatonin (Mel) on As-induced neurotoxicity. Thirty male Wistar rat were treated daily for 28 consecutive days. As (15 mg/kg, gavage) and Mel (10 and 20 mg/kg, i.p.) were administered to rats. Morris water maze test was done to evaluate learning and memory impairment in training days and probe trial. Oxidative stress markers including MDA and GSH levels, SOD activity, and HO-1 levels were measured. Besides, the levels of apoptosis (caspase 3, Bax/Bcl2 ratio) and autophagy markers (Sirt1, Beclin-1, and LC3 II/I ratio) as well as the expression of miR-144 and miR-34a in cortex tissue were determined. As exposure disturbed learning and memory in animals and Mel alleviated these effects. Also, Mel recovered cortex pathological damages and oxidative stress induced by As. Furthermore, As increased the levels of apoptosis and autophagy proteins in cortex, while Mel (20 mg/kg) decreased apoptosis and autophagy. Also, Mel increased the expression of miR-144 and miR-34a which inhibited by As. In conclusion, Mel administration attenuated As-induced neurotoxicity through anti-oxidative, anti-apoptotic, and anti-autophagy mechanisms, which may be recommended as a therapeutic target for neurological disorders.

Canine myxoid liposarcoma in Iran: a clinical report.

A 15-year-old male terrier dog with symptoms of lethargy and severe abdominal distension was referred to the polyclinic hospital of the Ferdowsi University of Mashhad, Mashhad, Iran. In addition to numbness and abdominal distension, the dog also had anorexia and severe weakness and some skin masses were observed. Due to the enlarged abdomen, splenomegaly was diagnosed in ultrasonography. Fine needle aspiration was performed on the liver and skin mass and then, neoplastic lesions were reported based on cytology. On the necropsy, two masses were found on the liver and shoulder skin. These masses were well-encapsulated, soft and multi-lobulated. Samples taken from the liver and skin were prepared by Hematoxylin and Eosin staining and then, two different immunohistochemical markers were used to confirm the initial diagnosis. Histopathological examination of these two well-encapsulated, soft and multi-lobulated masses on the liver and skin showed lipid content and liposarcoma was indicated. Immunohistochemical staining using two markers, S100 and MDM2, made a definitive diagnosis and confirmed the diagnosis.

Melatonin ameliorates arsenic-induced cardiotoxicity through the regulation of the Sirt1/Nrf2 pathway in rats.

Chronic arsenic (As) exposure, mainly as a result of drinking contaminated water, is associated with cardiovascular diseases. Mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and autophagy have been suggested as the molecular etiology of As cardiotoxicity. Melatonin (Mel) is a powerful antioxidant. Mel improves diabetic cardiomyopathy, cardiac remodeling, and heart failure. Following pre-treatment with Mel (10, 20, or 30 mg/kg/day i.p.), rats were orally gavaged with As (15 mg/kg/day) for 28 days. Electrocardiographic findings showed that Mel decreased the As-mediated QT interval prolongation. The effects of As on cardiac levels of glutathione (GSH) and malondialdehyde (MDA) were reversed by Mel pretreatment. Mel also modulated the Sirt1 and Nrf2 expressions promoted by As. Mel down-regulated autophagy markers such as Beclin-1 expression and the LC3-II/I ratio. Moreover, the cardiac expression of cleaved-caspase-3 and Bax/Bcl-2 ratio was decreased by Mel pretreatment. Reduced expression of miR-34a and miR-144 by As were reversed by Mel. The histopathological changes of cardiac injury associated with As exposure was moderated by Mel. Mel may improve As-induced cardiac dysfunction through anti-oxidative, anti-apoptotic, and anti-autophagic mechanisms.

Interactive effect of exercise training and growth hormone administration on histopathological and functional assessment of the liver in male Wistar rats.

BACKGROUND: Abuse of growth hormone (GH) is expanding in exercising populations due to its lipolytic and anabolic actions. The purpose of this study was to examine the interactive effect of exercise training and GH administration on histopathological and functional assessment in the liver of male Wistar rats. METHODS: Forty-eight male Wistar rats were randomly divided into six groups including control + saline group (CS), GH injection group (GI), resistance training + saline group (RS), aerobic training + saline group (AS), resistance training + GH injection group (RG), aerobic training + GH injection group (AG). All groups were injected with either saline or GH 1 h before each training session. RT and AT were performed five days/week for a total of 8-weeks. At the end of the study, blood samples and liver tissue samples were taken to evaluate circulating AST, ALT, and ALP enzymes, as well as albumin protein. Histopathology of liver tissue was performed via qualitative microscopic evaluation. RESULTS: Microscopic evaluation of liver tissue did not show any histopathologic changes. All the groups administered with GH showed a significant increase in ALT, ALP, and albumin protein (P<0.05). However, AST enzyme concentrations increased significantly only in the RG group (P=0.022). In addition, neither RS nor the AS groups showed significant AST, ALT, and ALP changes, but serum albumin concentration significantly increased in the AS group (P=0.033). CONCLUSIONS: The elevation of liver enzymes showed that GH administration with or without exercise training might cause severe liver damage.

Melatonin improves arsenic-induced hypertension through the inactivation of the Sirt1/autophagy pathway in rat.

Arsenic (As), a metalloid chemical element, is classified as heavy metal. Previous studies proposed that As induces vascular toxicity by inducing autophagy, apoptosis, and oxidative stress. It has been shown that melatonin (Mel) can decrease oxidative stress and apoptosis, and modulate autophagy in different pathological situations. Hence, this study aimed to investigate the Mel effect on As-induced vascular toxicity through apoptosis and autophagy regulation. Forty male rats were treated with As (15 mg/kg; oral gavage) and Mel (10 and 20 mg/kg, intraperitoneally; i.p.) for 28 days. The systolic blood pressure (SBP) changes, oxidative stress markers, the aorta histopathological injuries, contractile and relaxant responses, the level of apoptosis (Bnip3 and caspase-3) and autophagy (Sirt1, Beclin-1 and LC3 II/I ratio) proteins were determined in rats aorta. The As exposure significantly increased SBP and enhanced MDA level while reduced GSH content. The exposure to As caused substantial histological damage in aorta tissue and changed vasoconstriction and vasorelaxation responses to KCl, PE, and Ach in isolated rat aorta. The levels of HO-1 and Nrf-2, apoptosis markers, Sirt1, and autophagy proteins also enhanced in As group. Interestingly, Mel could reduce changes in oxidative stress, blood pressure, apoptosis, and autophagy induced by As. On the other hand, Mel led to more increased the levels of Nrf-2 and HO-1 proteins compared with the As group. In conclusion, our findings showed that Mel could have a protective effect against As-induced vascular toxicity by inhibiting apoptosis and the Sirt1/autophagy pathway.

Protective Role of Angiotensin II Type 1 Receptor Blocker on Short Time Effect of Oleic Acid Induced Lung and Kidney Injury.

BACKGROUNDS: Acute respiratory distress syndrome (ARDS) causes high mortality rate in clinic, and the pathogenesis of this syndrome may interact with renin angiotensin system (RAS) components. The main objective of this study was to determine the protective role of AT1R antagonist (losartan) on oleic acid (OA) induced ARDS and kidney injury. METHODS: The animal model of ARDS was performed by intravenous administration of 250 µl/kg oleic acid (OA). Male and female rats were subjected to received intravenously vehicle (saline, groups 1 and 4), OA (groups 2 and 5), or losartan (10 mg/kg) plus OA (groups 3 and 6), and six hour later, the measurements were performed. RESULTS: Co-treatment of OA and losartan increased the serum levels of blood urea nitrogen significantly (P < 0.05) and creatinine insignificantly in both gender. However, the OA induced kidney damage was decreased by losartan significantly in male (P < 0.05) and insignificantly in female rats. In addition, co-treatment of OA and losartan decreased lung water content significantly in male rats (P < 0.05). Based on tissue staining, no significant difference in lung tissue damages were observed between the groups, however some exudate were observed in lung male rats treated with OA alone which were abolished by losartan. CONCLUSIONS: Losartan may protect the kidney and lung against OA induced tissue injury in male rats. This protective action is not certain in female rats.

Necroptosis triggered by ROS accumulation and Ca2+ overload, partly explains the inflammatory responses and anti-cancer effects associated with 1Hz, 100 mT ELF-MF in vivo.

Whereas the anti-neoplastic activity of extremely low frequency magnetic fields (ELF-EMF) is well-documented in literature, little is known about its underlying anti-cancer mechanisms and induced types of cell death. Here, for the first time, we reported induction of necroptosis, a specific type of programed necrotic cell death, in MC4-L2 breast cancer cell lines following a 2 h/day exposure to a 100 Hz, 1 mT ELF-EMF for five days. For in vivo assessment, inbred BALB/c mice bearing established MC-4L2 tumors were exposed to 100 mT, 1 Hz ELF-EMF 2 h daily for a period of 28-day, following which tumors were dissected and fixed for evaluation of tumor biomarkers expression and types of cell death induced using TUNEL assay, Immunohistochemistry and H&E staining. Peripheral blood samples were also collected for assessing pro-inflammatory cytokine profile following exposure. An exaggerated proinflammatory response evident form enhancement of IFN-γ (4.8 ± 0.24 folds) and TNF-α (3.1 ± 0.19 folds) and number of tumors infiltrating lymphocytes (TILs), specially CD8+ Th cells (~20 folds), proposed occurrence of necroptosis in vivo. Meanwhile, exposure could effectively suppress tumor growth and expression of Ki-67, CD31, VEGFR2 and MMP-9. In vitro studies on ELF-EMF exposed MC-4L2 cells demonstrated a meaningful increase in phosphorylation of RIPK1/RIPK3/MLKL proteins and cleavage of caspase-9/caspase-3, confirming occurrence of both necroptosis and apoptosis. Complementary in vitro studies by treating ELF-EMF exposed MC-4L2 cells with verapamil (a calcium channel inhibitor), N-acetyl cysteine (a ROS scavenger) or calcium chloride confirmed the role of elevated intracellular calcium and ROS levels in ELF-EMF induced necroptosis.

Ameliorative Effects of Caffeic Acid Against Arsenic-Induced Testicular Injury in Mice.

Arsenic (As) is an environmental pollutant with destructive effects on different body organs, including the testis. This work was aimed to assess the ameliorative role of caffeic acid (CA) against As-provoked testicular damage in mice. Twenty-four adult male mice (31 ± 9 g) were randomly allocated to four equal groups. The first group served as control and was provided basal diet and tap water. Animals in the second group received water containing 200 ppm arsenite. The third group of mice received CA (60 mg/kg body weight; i.p.) during exposure to arsenite. Animals in the fourth group received CA. At the end of the experiment period (21 days), blood and testicular tissue sampling was done for biochemical and histopathological assessments. The results showed a significant decline of testicular ferric reducing antioxidant power (FRAP), superoxide dismutase, and glutathione peroxidase (GPx), as well as plasma concentrations of testosterone and dihydrotestosterone in As-treated mice compared to controls (p < 0.05). A significant increase in testicular malondialdehyde was also detected in group 2 relative to controls. Moreover, As exposure resulted in some morphological and histopathological alterations of the testis, including hyperemia, reduced tubular diameter and thickness of epithelial cell layers of seminiferous tubules, and Leydig cell necrosis. Simultaneous administration of CA plus As increased GPx, FRAP, testosterone, and dihydrotestosterone amounts and attenuated MDA levels as well as histopathological alterations to the levels that were not significantly different from those of the control group. These results indicate that caffeic acid can be suggested as an alleviative natural compound against As-induced damage in mice testes.

Evaluation of chromium accumulation and resulting histopathological changes in Libyan jirds (Mammals, Rodentia), affected by effluent from Ghazghan leather industrial town, Iran.

The leather industry is one of the major producers of wastewater, releasing large amounts of various chemicals into the environment. Chromium (Cr) is the most commonly used agent in the tanning industry. Accumulation in the animal body can adversely affect the functioning of animal tissues. The current study investigated the toxic effects of Cr on lung, kidney, liver, and testicular tissues in Libyan jirds (Meriones libycus) inhabiting the area surrounding Ghazghan leather industrial town, Mashhad, Iran. Average Cr concentrations were found to be significantly higher in samples from contaminated areas than controls (p < 0.05). The highest accumulation of Cr was found in lung tissue, while the liver tissue showed the lowest. The results also showed that sex and age had no significant effect on Cr accumulation in any tissue at either sampling area (p < 0.05). Histological analyses showed that Cr accumulation had caused changes in tissue samples from Libyan jirds from the contaminated area. Hyperemia was observed in all tissues. In kidney tissue, necrosis and degeneration of the epithelial cells of the tubules were seen as well, and in one case, we also observed hemorrhage. In liver tissue, necrosis, degeneration, and inflammation were observed, along with one case, of fibrosis. In lung tissue, we observed emphysema, hemorrhage, and inflammation. Testicular tissue also showed a considerable lesion. Given the proximity of specimens' habitat to an area of importance, i.e., the industrial town, and the species' dependence on its habitat for nutrition, Libyan jirds are particularly useful for monitoring. Thus, they can be used to monitor the level of contamination in future studies.

Melatonin inhibits Benzo(a)pyrene-Induced apoptosis through activation of the Mir-34a/Sirt1/autophagy pathway in mouse liver.

Benzo(a)pyrene (BaP), an important environmental pollutant, is produced as the result of incomplete combustion of organic materials in many industries and food cooking process. It has been purposed that BaP induces hepatotoxicity through oxidative stress and apoptosis. Several studies have shown that melatonin can protect against chemical-induced apoptosis through autophagy pathway. In this study, we assessed the modulating effect of melatonin, a well-known antioxidant, on BaP-induced hepatotoxicity through induction of autophagy. Thirty male mice were treated daily for 28 consecutive days. BaP (75 mg/kg; oral gavage) and melatonin (10 and 20 mg/kg, i.p.) were administered to mice. The liver histopathology and the levels of apoptosis and autophagy proteins as well as the expression of miR-34a were determined. The BaP exposure induced severe liver histological injury and markedly enhanced AST, ALT and MDA level. Also, apoptosis proteins and hepatic miR-34a expression increased. However, the level of Sirt1 and autophagy markers such as LC3 II/I ratio and Beclin-1 reduced. The co-administration of melatonin reversed all changes caused by BaP. In summary, melatonin appears to be effective in BaP-induced hepatotoxicity maybe through the miR-34a/Sirt1/autophagy molecular pathway.

Comparison of the serum level of interleukin-4 in patients with brucellosis and healthy controls.

INTRODUCTION: Evaluation of cytokines such as interleukin-4 (IL-4) can be an important tool in examining immune responses to brucellosis. Also, determining the response rate to treatment is necessary for controlling and eradicating of disease. The review of previous studies reveals contradictory results that require further research in this regard. The aim of this study was to compare the serum level of IL-4 in patients with brucellosis and healthy controls. MATERIAL AND METHODS: In this descriptive-analytical study for comparison of two groups, a total of 165 participants, including 83 patients with brucellosis and 82 non-infected people, were evaluated after matching of sex and age in Hamadan (northwest of Iran) in 2017 and the serum level of IL-4 was compared by ELISA method. The collected data were analyzed by SPSS software version 21 at 95% significant level. RESULTS: Mean of age in the case and control groups were 50.25 ± 16.01 and 43.26 ± 15.6 years, respectively. The serum levels of IL-4 in the case and control groups were 1.42 ± 0.51 pg/mL and 1.31 ± 1.02 pg/mL, respectively. Based on the non-parametric Mann-Whitney test, the IL-4 level was significantly higher in the case group, compared with the control (P < .001), but no statistically significant relationship was found between serum levels of IL-4 with age, sex, and serologic titers of Wright and 2ME. CONCLUSION: In patients with brucellosis, the level of IL-4 increases independently of the duration and severity of the disease, which indicates the role of this cytokine of immune system in this infectious disease.

The comparison of therapeutic effect of Clobetasol propionate lotion and squill extract in alopecia areata: a randomized, double-blind clinical trial.

Alopecia areata is a chronic inflammatory disease that characterized by round or oval patches of non-scarring hair loss. From the past, Urginea maritima (white squill) was used for the treatment of hair loss in Iranian traditional medicine. We aimed the comparison of Clobetasol lotion and squill extract efficacy in treatment of alopecia areata in a randomized, double-blind clinical trial. The 42 patients were randomized into two groups. Both groups received topical squill and clobetasol lotion twice daily lotion for 12 weeks. Clinical evaluation included size of patches (using 1×1 cm2 schablone), total number of grown hair and number of terminal hair was performed every 2 weeks. Re-growth of terminal coarse hairs was evaluated using a semi-quantitative regrowth score (RGS) (0: no regrowth, 1: growth of <25%, 2: growth of 25-50%, 3: growth of 51-75%, 4: growth of >75%). There were significant differences between RGS4 in two groups after 2- and 3-month treatment (P<0.05). At the end of follow-up period, the mean hair growth rates increased significantly from 6.5 to 11.3 in squill group (P = 0.031) and it improved significantly from 10.3 to 17.9 in clobetasol group (P = 0.001). There were no significant differences between mean hair growth rates in two groups after 3-month treatment (P = 0.969). The lotion 2% of U. maritima bulbs extract showed good effect in 45% patients with patchy alopecia areata and showed moderate effect on re-growth of terminal hairs.

A study on the concentration of heavy metals and histopathological changes in Persian jirds (Mammals; Rodentia), affected by mining activities in an iron ore mine in Iran.

Mining activity constitutes a potential source of heavy metal pollution in the environment. Long-term exposure to heavy metals (e.g., cadmium) has adverse health effects. Rodents frequently serve as bioindicators to monitor the levels of heavy metals in the environment. In the present study, concentrations of 10 heavy metals (Cd, Co, Cr, Cu, Fe, Mo, Ni, Pb, Sb, and Zn) in kidney, liver, and muscle tissue of the Persian jird (Meriones persicus) were evaluated. This is the first study to examine the histopathological changes in Persian jird tissues caused by the bioaccumulation heavy metals. The samples were taken at location that surrounded by Sangan Iron Ore Mine (SIOM) mining activities, in northeastern Iran. The results show that the highest concentrations for the metals were observed in kidney and liver, whereas lowest concentrations were found in muscle of Persian jirds. The concentration of Pb was below the limit of detection. Sex and age were two factors that could explain the different levels of heavy metal bioaccumulation, which affects the concentration of some metals. Adults had significantly higher Cu and Cd levels compared to juveniles. Males bioaccumulated more Zn in their kidneys than females, whereas females bioaccumulated more Fe in their livers. As expected, heavy metals affected various organs of the studied specimens. Hyperemia, hemorrhage, necrosis, and degenerative damage to the epithelial cells of the tubules, the presence of hyaline casts, and in one case, mononuclear leukocyte infiltration, were observed in samples of renal tissue. Hemorrhage and hepatocyte vacuolization were the most common histopathological changes found in samples of hepatic tissue. These effects and the concentrations of heavy metals in the studied specimens indicate the need for monitoring and frequent sampling to evaluate long-term persistent pollutants.