rat

Ovarian torsion is a critical gynecological emergency caused by the twisting of the ovary around its supporting structures, resulting in compromised blood flow and potential ovarian damage. Ovarian torsion/detorsion (T/D) can lead to severe complications, including infertility, if not promptly addressed. This study aimed to investigate the therapeutic effects of casticin (CAST) on ovarian and lung tissue injuries induced by a bilateral ovarian T/D model in rats. Experimental animals were randomly allocated into groups of sham, T/D, CAST 5 mg/kg, and CAST 10 mg/kg. Ovarian and lung tissues were subjected to biochemical, histopathological, and immunohistochemical analyses. In the T/D group, markers of oxidative stress and inflammation, including myeloperoxidase (MPO) activity, malondialdehyde (MDA), oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), and 8-hydroxy-2’ deoxyguanosine (8-OHdG), were significantly elevated (P<0.05). Conversely, superoxide dismutase (SOD) activity and total antioxidant status (TAS) levels were notably decreased (P<0.05). CAST administration significantly attenuated tissue damage by reducing oxidative stress and inflammatory markers while enhancing antioxidant defense (P<0.05). CAST demonstrated a therapeutic effect against ovarian and lung tissue damage induced by T/D, suggesting that it may serve as a potential therapeutic agent for treating ovarian T/D-related injuries. These findings underscore the potential of CAST in clinical settings, particularly as a novel intervention to mitigate complications associated with I/R injuries in gynecological emergencies.

Ulcerative colitis is a chronic recurrent inflammatory bowel disease of unknown etiology. The anti-inflammatory, immunomodulatory, and antioxidant characteristics of Henna (Lawsonia inermis) fixed oil (HFO) imply that it may be advantageous for the treatment of colitis.

In this research, the effect of HFO in a Wistar albino rat model of acetic acid (AA)-induced ulcerative colitis, was examined. The animals received daily oral administration of either normal saline (10 ml/kg), HFO (100, 400, and 1600 µl/kg), or dexamethasone (2 mg/kg) for 5 days. A single intracolonic injection of 2 ml of a 4% (v/v) acetic acid solution was used to induce colitis. The levels of myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α) were measured.

The administration of HFO at doses 400 and 1600 μl/kg showed a significant enhancement in the weight-to-length ratio of colon tissue in comparison to the control group. Furthermore, the increased amounts of HFO (400 and 1600 μl/kg) were associated with a significant reduction in ulcer severity, area, and index. However, examination of tissue samples revealed a decrease in the overall colitis index suggesting fewer inflammatory cells invaded the colonic regions of rats treated with HFO at doses of 400 and 1600 μl/kg. Moreover, the elevated MPO levels and TNF-α were significantly decreased following the administration of the fixed oil at these doses.

These findings indicate that HFO could potentially decrease the manifestations of experimental colitis in a dose-dependent manner.

Psoriasis is a chronic skin disease that usually manifests as white and silver spots on the skin. Because of its anti-inflammatory properties, we investigated the effects of ivermectin (IVM) on imiquimod (IMQ)-induced psoriasis in rats. Fifteen rats were assigned to 3 different groups (n=5 per group): the control group received normal water and food; the psoriasis group, in which psoriasis was induced by topical application of IMQ (1 mg per rat), and treatment group where rats were treated daily with topical IVM-gel (1%) from day 3 to 7. The Psoriasis Area Severity Index (PASI) Score for the entire treatment period was used to assess erythema, silver scale, and skin thickness on the dorsal region of rats, and the spleen-to-body weight index on day 7 was examined. Moreover, histological assessment of skin tissues was performed using fluorescence immunostaining and hematoxylin-eosin (H&E) staining.  The severity of lesions in the ivermectin group was reduced compared to the IMQ group, with a significant decrease in the average PASI scores. The results of fluorescence immunostaining showed that topical administration of IVM-gel reduced inflammation by decreasing Toll-like receptor 4 (TLR4) levels and p65 nuclear factor kappa-B (NF-κB). Furthermore, findings from H&E staining revealed that IVM-gel decreased dermal fibrosis, epidermal thickness, and infiltration of inflammatory cells caused by IMQ.  Based on the obtained results, it can be concluded that IVM-gel can effectively reduce psoriasis lesions due to its therapeutic properties, such as anti-inflammatory effects via targeting TLR4/p65 NF-κB.

Exercise and dietary supplementation influence various biomarkers of myocardial cell damage differently. This study aims to examine the effects of eight weeks of resistance training combined with spirulina supplementation on changes in cardiac troponin T (cTnT), brain natriuretic peptide (BNP), and creatine kinase-myocardial band (CK-MB) to assess myocardial damage.  Thirty-two male Sprague-Dawley rats (150±20 g, 9 weeks old) were randomly assigned into four groups: control (CO), resistance training (RT), spirulina supplementation (SP), and resistance training with spirulina supplementation (RTS). Spirulina was orally administered to SP and RTS groups at a dose of 200 mg/kg/day—the RT protocol involved climbing a 1-meter-high ladder over eight weeks. The cTnT, BNP, and CK-MB expression levels were quantified using real-time PCR.  Eight weeks of resistance training led to a significant increase in cTnT (p=0.044), BNP (p=0.001), and CK-MB (p=0.015) levels. In contrast, spirulina supplementation, both alone and combined with resistance training, significantly reduced cTnT (SP: p=0.005; RTS: p=0.001) and BNP (SP: p=0.002; RTS: p=0.0001) levels, with a more significant reduction observed in the RTS group. CK-MB levels also decreased in the SP group (p=0.001) and showed a non-significant trend in the RTS group (p=0.115).  Spirulina supplementation mitigates myocardial damage during resistance training by reducing biomarkers indicative of myocardial injury. These findings suggest that spirulina could be a protective agent against cardiac stress induced by resistance exercise.

Cyclophosphamide (Cy) as an alkylating chemotherapeutic agent with broad-spectrum efficacy in cancer treatment. Despite its wide spectrum of clinical usage, off-target multiple organ toxicity such as sperm and testicular injury is one of its toxic side effects. Since the Nasturtium officinale L. hydroalcoholic extract (NOE) contains a wide range of phytochemicals with various biological functions, the current study was designed to explore the protective potential of NOE on testicular toxicity caused by Cy in rats.

Forty-eight adult male Wistar rats were randomly allocated into eight groups (n=6): control, Cy [received a single dose of 75 mg/kg, intraperitoneal (i.p)], NOE+Cy (Prevention): received NOE 500 and 1000 mg/kg/day, orally for 21 consecutive days and on the last day received Cy, Cy+NOE (Treatment): received NOE 500 and 1000 mg/kg/day, orally for 7 days after Cy administration for 21 consecutive days, and NOE (500 and 1000 mg/kg/day). After experiments, the testicular weight and volume, testosterone level, and sperm parameters as well as histologic and histomorphometric changes of testis were examined.

Base on the results, Cy caused significant decreases in testicular weight and volume, decreased testosterone level and reduced sperm count, and motility whereas increased sperm abnormality (p<0.05). Cy significantly reduced seminiferous tubules diameter, and height of the seminiferous epithelium (p<0.05). Furthermore, disorganization of seminiferous tubules diameter was increased in Cy group (p<0.05). Interestingly, pre and post-treatment with NOE could effectively improve testicular weight and volume, and testosterone level as well as sperm parameters. Furthermore, NOE administration ameliorated seminiferous tubules diameter diameter, seminiferous epithelium height (p<0.05).

It is concluded that NOE may provide a potential protective effect for Cy-induced testicular damage.

 Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by β-cell dysfunction, insulin resistance, and elevated blood sugar levels. Several studies have explored the therapeutic potential of coenzyme Q10 (CoQ10) in managing diabetes, but no reports have examined the possible mechanism of CoQ10 in T2DM. Here, we reported that CoQ10 protects pancreatic β-cell structure and function by modulating the expression of mir-33a/ mir-21/SREBP1 and described more detailed tissue alterations. 

The study randomly divided rats into three groups (n = 10): control, diabetic, and diabetic + CoQ10. The diabetic + CoQ10 group consisted of diabetic rats that were concurrently administered CoQ10 (20 mg/kg/i.p.) three days/week for eight weeks. In addition to microscopic examination, the study involved evaluating glucose, insulin, and oxidative profiles in the serum and analyzing the levels of cholesterol, mir-33a, mir-21, and SREBP1 in pancreatic tissue. 

Our results revealed that CoQ10 restores glucose/insulin homeostasis, oxidative parameters, cholesterol levels, and the expressions of mir-33a, mir-21, and SREBP1. In addition, the CoQ10-treated diabetic rats showed increased active β-cells compared to the diabetic group. The immunohistochemical examination of insulin revealed a higher quantity and larger size of pancreatic islets in the experimental group.

The restoration of ߚ-cell integrity following treatment with CoQ10 may elucidate the therapeutic benefits of this compound in diabetes management, potentially through its influence on the pancreatic expression of mir-33a/mir-21/SREBP1, subsequently maintaining healthy tissue.

Chemotherapy with doxorubicin (DOX) is associated with toxicity in many organs including cardiac tissue. A large body of evidence has suggested that phenolic acids, such as protocatechuic acid (PCA), have beneficial effects on cardiovascular problems. This investigation was conducted to evaluate the ameliorative properties of PCA against DOX-induced cardiotoxicity in Wistar rats.

Experimental approach: 

Animals were treated with PCA (50, 100, and 200 mg/kg, orally) for 10 days. On the 7th day, a single injection of DOX (20 mg/kg/day, i.p.) was administered to induce cardiotoxicity. Electrocardiography, biochemical analysis of cardiac markers, and histological inspections were performed.

Pretreatment with PCA, especially at the doses of 100 and 200 mg/kg for 7 days before the administration of DOX, significantly improved cardiac rhythm and pathological changes, reduced serum levels of creatine phosphokinase-MB, lactate dehydrogenase, aspartate aminotransferase, lipid peroxides and also prevented heart weight rise.

Conclusions and implications:

 The in-vivo findings of the current study revealed that PCA exhibits protective effects against DOX-induced cardiotoxicity. These results suggest that PCA, a natural phenolic acid, may serve as a promising candidate for cardioprotective interventions in clinical trials involving chemotherapy with DOX.

To date, different strategies have been used for co-transplantation of cell-loaded biomaterials for bone tissue regeneration. This study aimed to investigate the osteogenic properties of adipose-derived-mesenchymal stem cell (AD-MSC) sheets combined with nanofibrous poly-caprolactone (PCL) mat and Gelfoam in rats with calvarial bone defect.

Calvarial critical-size defects were induced in male rats. Animals were classified into Control, Gelfoam, Gelfoam/PCL nanofiber, Gelfoam/AD-MSC sheet, and Gelfoam/PCL nanofiber/AD-MSC sheet groups. After 3 months, rats were sacrificed and the regeneration rate was evaluated.

Almost all groups showed bone regeneration properties, but the volume of newly formed bone was higher in groups that received Gelfoam/AD-MSC and Gelfoam/PCL nanofiber/AD-MSC sheets (P < 0.05). The application of Gelfoam/PCL nanofiber/AD-MSC sheets not only increased bone thickness, bone volume/total bone volume (BV/TV) ratio, strong Hounsfield Unit (HU), but also led to the formation of ossified connective tissue with wrinkled patterns.

The current study indicated that the Gelfoam/PCL nanofiber/AD-MSC sheet provides a suitable platform for effective osteogenesis in calvarial bone defects.

Inflammation is a natural defense mechanism, but it also plays a role in many chronic diseases such as diabetes, obesity, and cancer. While drugs like indomethacin are commonly used to reduce inflammation, their long-term use can lead to side effects. Lichens, as natural organisms, contain bioactive compounds that may reduce inflammation while minimizing side effects.

To assess the anti-inflammatory effects of lichen extracts at different doses and compare their efficacy with indomethacin in reducing inflammation in a carrageenan-induced rat model.

A total of 30 male albino Wistar rats, each weighing between 200 - 250 g, were randomly assigned into five groups of six animals. Groups 1 - 3 were administered the test extract at doses of 20, 40, and 80 mg/kg, respectively. Group 4 served as the positive control and received indomethacin at 10 mg/kg, while group 5, the negative control, received an equivalent volume of normal saline (vehicle). All treatments were administered prior to the induction of inflammation. Inflammation was elicited via intraplantar injection of 100 µL of a 1% (w/v) carrageenan solution prepared in 0.9% normal saline. We measured paw volumes using a plethysmometer at baseline (time zero) and again at 1, 2, 3, 4, and 5 hours after the carrageenan injection. Changes in paw volume relative to the baseline were recorded to evaluate the anti-inflammatory effects of the treatments.

The study demonstrated that increasing doses of the lichen extract significantly reduced paw swelling, particularly at the 80 mg/kg dosage. However, the lichen extract was not as strong as indomethacin. Still, the natural extract could be a safer option for long-term use because it likely causes fewer side effects than synthetic drugs.

Lichen extracts have good potential as a safer alternative to drugs like indomethacin for reducing inflammation. More research is needed to explore higher doses, understand how the extracts work, and improve their formulations to make them more effective.

Renal ischemia-reperfusion (RIR) induces kidney tissue damage by increasing oxidative stress, inflammation, and apoptosis.

This study investigated the protective effects of thyme essential oil (TEO) in mitigating oxidative stress in the kidney tissue using an RIR model.

Rats were randomly assigned to four groups (n = 8): (1) Sham, (2) IR, (3) IR+TEO, and (4) TEO. The TEO was administered at a dose of 0.5 mL/kg once daily for seven days before IR surgery. Renal ischemia was induced by clamping the kidney pedicle for 45 minutes, followed by 24 hours of reperfusion. Animals were then anesthetized, and serum samples were collected to measure urea and creatinine levels. Biochemical markers in kidney tissue, including malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPX), and paraoxonase 1 (PON1), were assessed. Histopathological and stereological examinations of kidney tissue were performed. Additionally, the expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-3 genes were analyzed.

Ischemia-reperfusion significantly increased serum urea and creatinine levels, MDA, MPO, inflammatory cytokine expression, caspase-3 gene expression, kidney tissue damage, and necrosis (P < 0.05). Antioxidant enzyme activity significantly declined after IR (P < 0.05). The TEO administration significantly reduced serum urea and creatinine levels, MDA, MPO, IL-6, and TNF-α in damaged kidney tissue compared to the IR group (P < 0.05). Furthermore, TEO significantly enhanced antioxidant enzyme activity compared to the IR group (P < 0.05).

The TEO exhibits antioxidant and anti-inflammatory properties, effectively reducing oxidative stress and inflammation in the RIR model.

Peripheral nerve disorders are the most common neurologic complications in humans. Therefore, any effective intervention to treat or reduce the complications of these disorders can be helpful. This study aimed to evaluate the effect of hesperetin on the experimental (crushed) sciatic nerve injury in the rat models.

In this experimental study, 60 adult male rats were studied in five groups (n = 12/each). The sham group (without nerve injury and treatment), the control group (with untreated nerve injury), and three experimental groups with injured sciatic nerve received oral hesperetin (100, 200, and 400 mg/kg, respectively) by gavage. All rats were euthanized on second and fourth post-treatment weeks for histopathological assessment of the sciatic nerve.

The results showed increased perineurium formation in the experimental group treated with 400 mg/kg hesperetin and a decrease in leukocyte infiltration in the experimental groups treated with 200 and 400 mg/kg hesperetin compared with the controls on second and fourth post-treatment weeks (P < 0.05). At the end of the second week, axon swelling significantly decreased in the group treated with 400 mg/kg hesperetin than the control group (P < 0.05). In addition, a decrease in the axonal count was observed in hesperetin-treated groups (200 and 400 mg/kg) after two weeks compared with the controls (P < 0.05).

The expression of the S100 gene in groups treated with 100 and 400 mg/kg hesperetin showed a significant decrease compared with the control group on days 14 and 28. Our findings indicated that hesperetin positively affects sciatic nerve repair in the rat model.

Formalin, as formaldehyde dissolved in water, is a carcinogen that causes oxidant and antioxidant imbalance. The metabolic products of formaldehyde, such as formic acid, stimulate oxidative stress, leading to kidney damage. Bidens pilosa L. (B. pilosa L.) leaves contain flavonoids with antioxidant and anti-inflammatory activities. The present study aimed to determine the nephroprotective effect of B. pilosa L. leaf extract on the histological structure and weight of the kidney organs of white rats (Rattus norvegicus) induced by formalin.

Rats were grouped into five treatment groups, including normal control, negative control, and three dose groups (25 mg/kg BW, 50 mg/kg BW, and 100 mg/kg BW). Rats were induced with formalin 0.2 ml/kg BW for 7 days orally, followed by dose treatment for 7 days. Kidney histology and weight were examined on day 14. Antioxidant and anti-inflammatory activities were predicted by molecular docking.

The kidney weight in the treatment was not significantly different, but histologically, the B. pilosa L. leaf extract could significantly reduce necrosis cells at a dose of 100 mg/kg to approach the score of the normal group. Secondary metabolites, such as isochlorogenic acid and luteolin, had antioxidant and anti-inflammatory properties, which contribute to therapy.

B. pilosa L. leaf extract can potentially protect nephrons with antioxidant and anti-inflammatory activities.

Polycystic ovarian syndrome (PCOS) is a prevalent hormonal disorder among women of reproductive age, resulting in female infertility. Researchers are exploring safe and affordable treatments for this disorder.

This study explored the therapeutic effects of fennel essential oil (FEO) and manganese (Mn) on hormonal and histological markers in rats with estradiol valerate-induced PCOS.

In this experimental study, 35 adult female Wistar rats (9 wk old, 200-250 gr) were divided into 7 groups. For 14 days, groups 1-4 received normal saline intraperitoneally, sesame oil intramuscularly, FEO intraperitoneally, and Mn orally, respectively. PCOS was induced in remaining groups through a single intramuscular injection of estradiol valerate. 60 days after induction, the 6th and 7th groups were treated individually with intraperitoneal FEO and oral Mn for 14 days. Blood samples were analyzed for estrogen, progesterone, and malondialdehyde (MDA) markers. The ovarian tissues were histologically examined to assess cyst formation and structural changes.

FEO significantly increased estrogen and progesterone levels in PCOS rats compared to the PCOS group (p ≤ 0.05). Mn also elevated progesterone levels, but the change was not statistically significant (p > 0.05). No significant differences in MDA levels were observed between the PCOS and PCOS+FEO groups. Although MDA levels decreased in the PCOS+Mn group, the reduction was not statistically significant (p > 0.05). Both FEO and Mn treatments significantly reduced ovarian cyst numbers compared to untreated PCOS rats (p ≤ 0.05).

FEO and Mn demonstrated potential in restoring hormonal balance and improving ovarian histology, offering promise as low-cost treatments for PCOS.

This article has been extracted from Pharm. D. Thesis. (Ensiyeh Mohebbi Kian)

Successful reproduction relies on a functioning hypothalamic-pituitary-gonad axis. Damage to this axis disrupts the estrus cycle and reproductive capability.

This study aimed to evaluate the effects of single or multiple platelet-rich plasma (PRP) injections on repairing the damaged hypothalamic arcuate nucleus (ARC) and restoring the estrus cycle in Wistar rats.

90 female Wistar rats (2-3 months old, 250-280 gr) with regular estrous cycles were divided into a control group and 8 experimental groups (n = 10/each). After bilateral stereotaxic chemical surgery of the ARC using quinolinic acid (500 nmol/2 μl), the experimental rats were categorized into several treatment regimens: ARC- (no treatment), 1 PRP injection (immediately, 24 hr, 48 hr, and 72 hr postsurgery), 2 PRP injections (immediately, 24 hr), 3 PRP injections (immediately, 24 hr, and 48 hr), and 4 PRP injections (immediately, 24 hr, 48 hr, and 72 hr). Vaginal smear cytology was performed daily for 2.5 months. In the end, rats brains were removed and divided for real-time polymerase chain reaction analysis of kisspeptin, neurokinin B, and dynorphin, as well as for ARC cell counting.

Vaginal smear cytology indicated that PRP administration gradually restored the estrous cycle. Compared to the ARC- group, PRP treatment significantly increased ARC cell density (p = 0.012) and mRNA levels of kisspeptin, neurokinin B, and dynorphin (p < 0.001).

These findings not only emphasized the importance of the ARC for the regularity of estrous cycle, but also showed the potential effects of local PRP treatment in contribution to the protection/reconstruction of ARC.
 

This article has been extracted from Ph.D. Thesis. (Elham Abbasi)