Piperine mitigates oxidative stress, inflammation, and apoptosis in the testicular damage induced by cyclophosphamide in mice.

Although cyclophosphamide (CP) has been approved as an anticancer drug, its toxic effect on most organs, especially the testis, has been established. Piperine (PIP) is an alkaloid that has antioxidant, antiapoptotic, and anti-inflammatory activities. This study was investigated the protective effects of PIP on CP-induced testicular toxicity in the mice. In this experimental study, 48 adult male BALB/c mice (30-35 g) were divided into six groups (n = 8), receiving normal saline (C), 5 mg/kg of PIP (PIP5), 10 mg/kg of PIP (PIP10), 200 mg/kg of CP, 200 mg/kg of CP + PIP5, and 200 mg/kg of CP + PIP10. On the eighth day of the study, blood and testis samples were prepared for serum testosterone hormone quantification, sperm analysis, histological, and immunohistochemical assays. The results of this study showed that CP induced testicular toxicity with the decrease of sperm count, motility, and viability. Also, CP treatment caused histological structure alterations in the testis, including exfoliation, degeneration, vacuolation of spermatogenic cells, and reducing the thickness of the epithelium and the diameter of the seminiferous tubule. In addition, CP decreased glutathione (GSH) levels, increased malondialdehyde (MDA) levels, Caspase-3, and NF-κB. At the same time, PIP treatment reduced testicular histopathological abnormalities, oxidative stress, and apoptosis that were induced by CP. These results showed that PIP improved CP-induced testicular toxicity in mice, which can be related to its antioxidant, antiapoptotic, and anti-inflammatory activities.

The effect of source animal age, decellularization protocol, and sterilization method on bovine acellular dermal matrix as a scaffold for wound healing and skin regeneration.

BACKGROUND: Healing the full-thickness skin wounds has remained a challenge. One of the most frequently used grafts for skin regeneration is xenogeneic acellular dermal matrices (ADMs), including bovine ADMs. This study investigated the effect of the source animal age, enzymatic versus non-enzymatic decellularization protocols, and gamma irradiation versus ethylene oxide (EO) sterilization on the scaffold. METHODS: ADMs were prepared using the dermises of fetal bovine or calf skins. All groups were decellularized through chemical and mechanical methods, unless T-FADM samples, in which an enzymatic step was added to the decellularization protocol. All groups were sterilized with ethylene oxide (EO), except G-FADM which was sterilized using gamma irradiation. The scaffolds were characterized through scanning electron microscopy, differential scanning calorimetry, tensile test, MTT assay, DNA quantification, and real-time PCR. The performance of the ADMs in wound treatment was also evaluated macroscopically and histologically. RESULTS: All ADMs were effectively decellularized. In comparison to FADM (EO-sterilized fetal ADM), morphological, and mechanical properties of G-FADM, T-FADM, and CADM (EOsterilized calf ADM) were changed to different extents. In addition, the CADM and G-FADM were thermally more stable than the FADM and T-FADM. Although all ADMs were noncytotoxic, the wounds of the FADM, T-FADM, and G-FADM groups were contracted to almost 30.0% of the original area on day 7, significantly faster than the CADM (17.5% ± 1.7) and control (12.2% ± 1.59) groups. However, by day 21, all ADMs were mostly closed except for the untreated group (60.1 ± 1.8). CONCLUSION: Altogether, fetal source and EO-sterilized samples performed better than calf source and gamma-sterilized samples unless in some mechanical properties. There was no added value in using enzymatic treatment during the decellularization process. Our results suggest that the age, decellularization, and sterilization methods of animal source should be selected based on the clinical requirements.

Febuxostat, an inhibitor of xanthine oxidase, ameliorates ionizing radiation-induced lung injury by suppressing caspase-3, oxidative stress and NF-κB.

Febuxostat (FBX), a selective inhibitor of xanthine oxidase, has several biological properties such as antioxidant, anti-inflammatory and anti-apoptosis activities. The purpose of this study was to evaluate the protective effect of FBX against ionizing radiation (IR)-induced lung injury through mitigation of oxidative stress, inflammation and apoptosis. Sixty-four mice were randomized into eight groups as control, FBX (5, 10, and 15 mg/kg), IR (6 Gy), and IR + FBX (IR + FBX in three doses). Mice were received FBX for 8 consecutive days and then were exposed to IR at a single dose (6 Gy) of X-ray. At 1 and 7 days after irradiation, the biochemical parameters were analyzed in lung tissue, while histological and immunohistochemical examinations were evaluated 1 week after irradiation. Irradiation led to elevate of oxidative stress parameters (an increase of MDA, PC, NO, and decrease of GSH), inflammation and apoptosis in lung of mice. Furthermore, IR resulted in histopathological changes in the lung tissues. These changes were significantly mitigated by FBX treatment. FBX also inhibited immunoreactivity of caspase-3, NF-κB, and reduced oxidative stress. This study showed that FBX is able to protect lung injury induced by IR through inhibiting apoptosis (caspase-3), oxidative stress and inflammation (NF-κB).

Protective effect of Feijoa sellowianan fruit on testicular toxicity-induced by cadmium chloride.

The purpose of the present study was to investigate the protective potential of Feijoa fruit extract on cadmium chloride (CdCl2 )-induced testicular injury and pituitary-gonadal axis. Adult male Wistar rats were randomly divided into four groups: (a) control (normal saline, orally), (b) cadmium chloride (0.1 mg/kg, single dose, intraperitoneally), (c) Feijoa fruit extract (400 mg/kg, orally for 30 consecutive days) and (d) CdCl2  + Feijoa fruit extract. One day after receiving the last medicine, the LH, FSH, prolactin and testosterone concentration were assayed. Also, sperm parameters and tissue structure of the testis were evaluated. Administration of Feijoa fruit extract after CdCl2 injection in rats ameliorated sperm parameters such as sperm count, morphology, motility and sperm viability, increased levels of LH, FSH, prolactin and testosterone and improved testicular histology. According to the results of this study, it was shown that Feijoa can reduce the destructive side effects of CdCl2 on testicular tissue and sex hormones of the pituitary-gonadal pathway.

Protective effects of sinapic acid against cyclophosphamide-induced testicular toxicity via inhibiting oxidative stress, caspase-3 and NF-kB activity in BALB/c mice.

Cyclophosphamide (CP), as a chemotherapeutic agent, with the generation of oxidative stress leads to testicular toxicity. Sinapic acid (SA), as a phenylpropanoid compound has therapeutic activities. This research was planned to evaluate the improving effects of SA versus testicular injury induced by CP. Forty-eight mice were distributed into six groups: untreated, SA (5 and 10 mg/kg), CP (200 mg/kg) and CP + SA (5 and 10 mg/kg). SA was administrated for 7 successive days and CP was administered intraperitoneally on the 3rd day of study. On the 10th day of research, testicular toxicity was evaluated by sperm parameters test, tissue (oxidative stress parameters) and serum (testosterone) biochemical, histopathological, and immunohistochemical (Caspase-3 and NF-kB) assays. The findings illustrated that CP induces atypical appearance in tissue structure, disorder of sperm parameters dysfunction, decrease of testosterone, oxidative stress (an increase of MDA and decrease of GSH), apoptosis and inflammation in testicular tissue. SA administration protected testis from oxidative stress and improves testosterone level and structure. Moreover, immunohistochemical findings also showed that SA can inhibit Caspase-3 and NF-kB activity. Data have confirmed that SA could protect testis structure and its functions against CP-induced injury through antioxidant, anti-inflammatory and anti-apoptotic activities.

Effect of prenatal exposure to Benzo[a]pyrene on ovarian toxicity and reproductive dysfunction: Protective effect of atorvastatin in the embryonic period.

As an environmental contaminant, Benzo[a]pyrene (B[a]P; BaP) disrupts the antioxidant signaling and thus leads to the induction of oxidative stress and the damage of DNA in the ovary. low-dose atorvastatin (ATV) has antioxidant and anti-apoptotic properties. The present study aimed to survey the effects of prenatal exposure to BaP on ovarian toxicity and also to investigate the protective role of ATV in reducing ovarian toxicity. In this study, rats were divided into seven groups: control, ATV (10 mg/kg), oil, BaP (10 and 20 mg/kg), and ATV + BaP (10 and 20 mg/kg). BaP and ATV were administrated from gestation day 7-16 (GD7 to GD16), orally. 10 weeks after the birth, female offsprings were examined for oxidative stress markers, sex hormones, ovarian and tubular tissue structure, and the apoptosis markers. Data showed that BaP significantly reduced glutathione, increased malondialdehyde level, and disrupted the tissue structure of the ovary. Moreover, estrogen and progesterone levels significantly decreased in the offsprings rats. Also, BaP increased caspase-3 immunoreactivity. Atorvastatin treatment along with BaP in the embryonic period were able to bring the antioxidant status and sex hormones levels relatively close to normal. Besides, histological findings showed that atorvastatin was able to improve ovarian and oviduct abnormalities caused by BaP. Based on the above studies be concluded that atorvastatin in the embryonic during was able to reduce ovarian damage caused by BaP with antioxidant and anti-apoptotic properties.

Gliclazide attenuates cisplatin-induced nephrotoxicity through inhibiting NF-κB and caspase-3 activity.

Cisplatin (CP), as a chemotherapeutic drug, causes nephrotoxicity that has limited the clinical utility of CP. Gliclazide (GLZ), as an antihyperglycemic drug, at low dose has antioxidant property. In this study, we aimed to investigate the protective effect of GLZ against CP-induced acute renal injury. Sixty-four BALB/c mice were randomly divided into eight groups. The groups were included as control, GLZ (5, 10, and 25 mg/kg), CP, and GLZ (5, 10, and 25 mg/kg) + CP. Renal function markers (serum creatinine and blood urea nitrogen), oxidative stress markers (malondialdehyde and glutathione), apoptotic marker (caspase-3), and NF-κB were histopathologically evaluated. The results of our study showed that increased urea and creatinine were evidence of CP-induced nephrotoxicity. Histopathological examination revealed tubular epithelial and Bowman degeneration, edema, and cytoplasmic vacuolation in renal tissue structure. Administration of GLZ reduced oxidative stress, caspase-3, and NF-κB activity, and improved kidney function markers in CP-treated mice compared with CP alone group. Also, we observed that the histological tissue structure of the kidney was maintained. GLZ at dose of 25 mg/kg had higher protective effect as compared with other doses. Overall, our study suggests that GLZ with antioxidant, antiapoptotic, and anti-inflammatory properties may be a promising new therapeutic agent to prevent CP-induced nephrotoxicity.

Preclinical pharmacokinetic, biodistribution, radiation dosimetry, and toxicity studies of 99mTc-HYNIC-(Ser)3-LTVPWY: A novel HER2-targeted peptide radiotracer.

Accurate assessment of the HER2 expression is an essential issue for predicting response to anti-HER2 therapy in breast cancer patients. The aim of this study was to evaluate 99mTc-HYNIC-(Ser)3-LTVPWY (99mTc-HYNIC-LY) peptide as a novel HER2-targeted radiolabeled peptide in healthy mice to examine the applicability of this imaging agent in a first-in-human clinical trial. To this end, pharmacokinetic and dosimetry studies were performed according to the ICH guideline M3 (R2) with 99mTc-HYNIC-LY. To estimate the radiation-absorbed doses in humans, the accumulated activity in each mouse organ was calculated based on biodistribution data. In addition, toxicology assessment was performed based on mortality events, body weights, and serum biochemical, hematological, and histopathological assays. The pharmacokinetic study showed rapid blood clearance. Based on the results of biodistribution study, the highest radioactivity was observed in the kidneys. The projected absorbed doses to the kidneys, liver, lungs, stomach, and spleen were obtained as 1.70E-02, 1.42E-02, 1.02E-02, 8.62E-03, and 8.34E-03 mSv/MBq, respectively. The results also revealed that serum biochemical and hematological parameters were in the normal range. No significant morphologic alterations were observed in the liver, kidneys, and spleen tissues. Consequently, the results were indicative of the suitability of 99mTc-HYNIC-LY peptide for advancement to a first-in-human clinical trial.

Juglans Regia L. Leaf Extract Attenuates Diabetic Nephropathy Progression in Experimental Diabetes: An Immunohistochemical Study.

BACKGROUND: There is accumulating evidence that Juglans regia L. (GRL) leaf extract has hypoglycemic and antioxidative properties. The present study aimed to investigate the protective effects of GRL leaf extract against diabetic nephropathy (DN). METHODS: In total, 28 male adult Sprague-Dawley rats were used. The DN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats received intragastric administration of GRL leaf extract (200 mg/kg/day) starting 1 week (preventive group) and 4 weeks (curative group) after the onset of hyperglycemia up to the end of the 8th week, whereas other diabetic rats received only isotonic saline (diabetic group) as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic nephropathy, various parameters of apoptosis and inflammation were assessed. Statistical analysis was performed using the SPSS software, version 15.0. The data were compared between the groups using the Tukey's multiple comparison test and the analysis of the variance. P values ˂0.05 were considered statistically significant. RESULTS: Fasting blood sugar (FBS) levels (P=0.001) and histopathological changes in the kidney of diabetic rats attenuated after GRL leaf extract consumption. Greater caspase-3 (P=0.004), COX-2 (P=0.008), PARP (P=0.007), and iNOS (P=0.005) expression could be detected in the STZ-diabetic rats, which were significantly (P=0.009) attenuated after GRL leaf extract consumption. In addition, attenuation of lipid peroxidation in the diabetic rats was detected after GRL consumption (P=0.01). CONCLUSION: GRL leaf extract exerts preventive and curative effects against diabetic nephropathy.

Protective effects of methanolic extract of Juglans regia L. leaf on streptozotocin-induced diabetic peripheral neuropathy in rats.

BACKGROUND: Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. METHODS: The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. RESULTS: Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. CONCLUSION: Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against neuropathy.

Effects of the combination of bone marrow stromal cells and exercise on corticosterone, BDNF, IGF-1, and anxiety-like behaviour in a rat model of post-traumatic stress disorder: Comparable effects of exercise.

AIM: Post-traumatic stress disorder (PTSD) requires more effective treatment options with fewer side effects. Stem cell therapy, as a novel approach, has been investigated in the treatment of various diseases, including brain disorders. This study investigated the effects of bone marrow stromal cells (BMSCs) and the combination of BMSCs with exercise on corticosterone, BDNF and IGF-1, and anxiety-like behaviours in a male rat model of PTSD. METHODS: Male adult Wistar rats were subjected to PTSD induced by the single prolonged stress (SPS) model. 7 days after SPS, BMSCs were injected intravenously. The exercise started on day 11 and continued for 4 weeks. On day 40th, anxiety behaviour, corticosterone, BDNF, and IGF-1 were tested. p < 0.05 was considered as a significant level. RESULTS: The study showed that a combination of BMSCs and exercise significantly reduced anxiety-related behaviours, and alterations in BDNF, IGF-1, and corticosterone levels. Also, BMSCs alone significantly reduced some of the PTSD-induced impairments. However, exercise alone showed greater efficiency in comparison with BMSCs alone. CONCLUSION: According to the results, although combination therapy effectively improved PTSD-related complications, exercise had relatively comparable effects on PTSD. Exercise has the potential to enhance the efficacy of BMSC therapy. Further research is required to determine whether BMSC therapy is sufficiently efficacious and safe in clinical settings.

The Potential Radioprotective Effect of Piperine against Radiation-Induced Lung Injury in Mice: Histopathological and Biochemical Evaluations.

INTRODUCTION: It has been hypothesized that piperine, the main alkaloid component of black pepper, possesses a unique radioprotective effect. This study aimed to investigate the protective effect of piperine against Radiation-Induced Lung Injury (RILI) in mice. METHOD: Firstly, eighty male mice were divided into eight groups; the control group did not receive any dosage of piperine and radiation (6 Gy), and the other groups received piperine alone at doses 10, 25, and 50 mg/kg, radiation, and radiation-piperine combination (6 Gy + 10, 25, and 50 mg/kg). Animals received piperine by gavage for 7 consecutive days. To investigate the effect of piperine pretreatment in mice that were exposed to radiation, histopathological and biochemical evaluations (markers of oxidative stress) were performed. Irradiation led to an increase in oxidative stress (increase in MDA and PC). Pretreatment of piperine in all three doses in irradiated mice was able to reduce oxidative stress compared to mice that were only exposed to radiation. RESULTS: Piperine at a dose of 25 mg/kg exhibited the highest protective effect as compared to other doses. Also, in the histopathological examination, it was seen that pretreatment with piperine was able to improve the infiltration of inflammatory cells and reduce the thickness of the alveolar septum and air sac damage. CONCLUSION: The outcomes completely proved significant lung protection by piperine in mice through reducing oxidative stress. This natural compound could be considered a protective agent against lung injury induced by ionizing radiation.

5-HT3 antagonist, tropisetron, ameliorates age-related renal injury induced by D-galactose in male mice: Up-regulation of sirtuin 1.

Objectives: The kidney ages faster than other organs due to changes in energy metabolism, mitochondrial dysfunction, and oxidative stress. This study looked into the anti-aging effect of tropisetron. Materials and Methods: D-galactose was administrated subcutaneously in a mouse model for eight weeks in order to induce renal aging. Three separate intraperitoneal doses of tropisetron (1, 3, and 5 mg/kg body weight) were given at the same time. We assessed markers of mitochondrial dysfunction, oxidative stress, and inflammation. Via Real-Time PCR, the expressions of genes linked to aging (SIRT1) and apoptosis (Bax and Bcl-2) were ascertained. In addition, an assessment of histopathological changes, blood urea nitrogen, and creatinine concentrations was done. Results: In kidney tissue, tropisetron reduces mitochondrial dysfunction and oxidative stress, which are caused by D-galactose-induced overproduction of inflammatory mediators. Additionally, tropisetron demonstrated antiapoptotic activity in renal tissue and augmented the decrease in SIRT1 gene expression associated with D-galactose administration. Besides, tropisetron significantly improved the histological alterations in the renal tissues of aged mice and effectively decreased the elevated levels of creatinine and also blood urea nitrogen. Conclusion: The results provided additional insight into the effect of tropisetron on renal aging and the underlying mechanisms, particularly through its ability to modulate SIRT1 signaling.

Luteolin-incorporated fish collagen hydrogel scaffold: An effective drug delivery strategy for wound healing.

In clinical practice, wound care has always been challenging. Hydrogels play a key role in facilitating active wound recovery by absorbing exudates, maintaining moisture, and alleviating pain through cooling. In this study, type I collagen was isolated from the skin of crucian carp (Carassius carassius) and verified by amino acid analysis, FTIR, and SDS-PAGE. By adopting a new approach, luteolin was added to collagen hydrogels in situ after being dissolved in an alkaline solution. XRD and SEM confirmed the luteolin was incorporated and entirely distributed throughout the hydrogel. The plastic compression improved the young's modulus of hydrogel to 15.24 ± 0.59 kPa, which is adequate for wound protection. The drug loading efficiency was 98 ± 1.47 % in the selected formulation. The luteolin-incorporated hydrogel enabled regulated drug release. We assessed the cytotoxicity using MTT and live-dead assays, as well as examined the hemocompatibility to determine the biocompatibility of the hydrogel. In vivo experiments showed that the hydrogel with luteolin had the highest wound closure rate (94.01 ± 2.1 %) and improved wound healing with granular tissue formation, collagen deposition, and re-epithelialization. These findings indicate that this efficient drug delivery technology can accelerate the process of wound healing.

The protective effect of benfotiamine on gastric ulcers in male rats: an experimental study.

Gastric ulcers are a common gastrointestinal disorder associated with significant morbidity and mortality. It can also increase the risk of gastric cancer. This study aimed to investigate the effect of benfotiamine on experimentally-induced gastric ulcers in male rats. In this study, 30 Wistar male rats were divided randomly into six groups: control (normal), indomethacin, omeprazole, and treatment groups, including 50, 100, and 200 mg/kg of benfotiamine. Gastric ulcer was induced by indomethacin gavage. Omeprazole and different therapeutic doses of benfotiamine were administered for three days. Twenty-four hours after the last treatment, the rats were euthanized, and samples were collected.The results demonstrated that 100 and 200 mg/kg of benfotiamine treatment significantly improved indomethacin-induced gastric tissue damage. Moreover, benfotiamine at 100 and 200 mg/kg effectively attenuated the levels of pro-inflammatory cytokines IL-6 and TNF-α and oxidative stress markers MDA and ROS while increasing the antioxidant GSH. These findings suggest that benfotiamine's gastroprotective effects are mediated through its antioxidant and anti-inflammatory properties, which help mitigate the tissue damage and inflammatory response associated with indomethacin-induced gastric ulcers.However, further research is needed to elucidate the precise molecular mechanisms underlying these beneficial effects and to evaluate the potential therapeutic application of benfotiamine in clinical settings.

Rutin mitigates perfluorooctanoic acid-induced liver injury via modulation of oxidative stress, apoptosis, and inflammation.

Objectives: Perfluorooctanoic acid (PFOA) is a persistent organic pollutant (POP), broadly present in the environment. Due to long biological half-life, it is accumulated in the body, especially the liver, causing hepatocellular damage. This study was designed to assess the effects of rutin on PFOA-induced liver damage in rats. Materials and Methods: Male Wistar rats were exposed to PFOA (10 mg/kg/day) alone, or in combination with different doses of rutin (25, 50, and 100 mg/kg/day) by oral gavage for 4 weeks. Results: PFOA altered the levels of liver enzymes, induced a notable change in the tissue structure of the liver, caused some levels of mitochondrial dysfunction, and increased the expression of pro-apoptotic and pro-inflammatory genes. Co-treatment with rutin mitigated the PFOA-induced elevation of liver enzymes, histopathological defects, oxidative damage, and mitochondrial dysfunction. In addition, rutin declined the stimulatory effects of PFOA on the Bax: Bcl2 ratio and reduced the PFOA-induced gene expression of TNF-α, IL-6, NF-ƙB, and JNK. Conclusion: These findings suggest rutin as a protective agent for PFOA-induced liver injury, albeit the protection was partial. Possible mechanisms are inhibition of oxidative stress, mitochondrial dysfunction, and inflammatory response.

Radioprotective effect of piperine, as a major component of black pepper, against radiation-induced colon injury: biochemical and histological studies.

BACKGROUND: Patients undergoing radiotherapy are prone to radiation-induced gastrointestinal injury. Piperine is an alkaloid component in black pepper with a unique chemopreventive activity against oxidative stress-related damage in healthy tissues. The purpose of this study was to investigate the effects of piperine on intestinal damage. METHODS: In this study, mice were divided into eight groups: including the control, piperine (10, 25, and 50 mg/kg), radiation (6 Gy), and piperine+radiation (10, 25 and 50 mg/kg + 6 Gy) groups. The radioprotective effects of piperine were evaluated by biochemical (MDA, GSH, and PC) and histopathological assessments in colon tissues. RESULTS: The 10 mg/kg dose of piperine significantly reduced the levels of oxidative stress biomarkers compared to the group that received only radiation. In addition, pre-treatment with 10 mg/kg piperine diminished the histopathological changes like vascular congestion in the submucosa, while the dose of 50 mg/kg led to the infiltration of inflammatory cells. CONCLUSION: Based on this study, it is concluded that piperine, at low dose, with its antioxidant properties, could reduce the colon damage caused by radiation.

Melissa Officinalis L. aqueous extract pretreatment decreases methotrexate-induced hepatotoxicity at lower dose and increases 99mTc-phytate liver uptake, as a probe of liver toxicity assessment, in rats.

OBJECTIVE: Hepatotoxicity remains amongst the restricting factors of Methotrexate (MTX)-associated cancer therapy, especially in high doses of chemo-drugs or prolonged treatment. Due to the known protective effects of Melissa officinalis (M. officinalis), the aqueous extract of this plant was evaluated to ameliorate MTX-associated hepatotoxicity in rats. METHODS: Adult female Wistar rats were received or not M. officinalis aqueous extract at doses of 100 mg/kg (for 14 and 24 consecutive days) and 2 g/kg (for 14 consecutive days) by gavage technique. MTX (20 mg/kg) was intraperitoneally injected on the 10th- and 20th-day post-M. officinalis treatment. 24 h after the last day of treatment, 99mTc-phytate was intravenously injected through the tail of rats. Animals were killed at 20 min after radiocolloid injection, and vital tissues including the liver and spleen were isolated, weighed, and their radioactivity was counted. As well, 99mTc-phytate scintigraphy and histopathology of the liver were performed for higher accuracy. RESULT: A significant increase in liver radioactivity was detected in M. officinalis+MTX receiving groups compared with the MTX rats which were more robust at a dose of 100 mg/kg for 14 days. Also, a significant reduction in liver radioactivity was evident with M. officinalis extract at a dose of 2 g/kg for 14 days in comparison with the control group, this reduction was not significant at the lower dose of 100 mg/kg. Gamma scintigraphy and histopathological examinations confirmed the hepatoprotective effect of M. officinalis vs MTX-induced liver injury in rats. CONCLUSION: In conclusion, we highlighted the liver uptake of 99mTc-phytate as a valuable method for assessment of liver toxicity and addressed that M. officinalis pretreatment (100 mg/kg for 14 days) ameliorates the MTX-associated hepatotoxicity in rats; however, M. officinalis itself induces liver toxicity at higher doses.

Comparative evaluation of the effect of three types of fixatives (formalin, Bouin and Carnoy) on histomorphological features of various viscera.

Tissue shrinkage is one of the problems in preparing tissue sections. This study compares the use of 10% formalin, Bouin and Carnoy as fixatives on several mouse tissues to determine histomorphological features. In this experimental study, liver, kidney, heart, lung, testicle, spleen, brain and cartilage tissues were isolated from five BALB/c mice. Then, they were fixed with three types of fixatives. After dehydrating, clarifying and embedding, all samples were stained with haematoxylin and eosin. Then, the tissue structure of the viscera was evaluated qualitatively. The results showed that each fixative is more suitable for evaluating a specific part of the tissue. However, relative shrinkage appeared in the tissue sections fixed with 10% Formalin, (1) in the heart as spaces between muscle fibre bundles, (2) in the liver as the dilation of the liver sinusoidal spaces, (3) in the kidney tissue as the expansion of the lumens of the convoluted proximal and distal tubules, (4) in the spleen as open spaces inside the red and white pulps and (5) in the brain as an increase in the space between the cells of the granular and pyramidal cell layers of the cortex. In tissues that were soft and fragile, such as testis, liver and brain, Bouin's fixative was more suitable. Carnoy's fixative was more suitable for the spleen and kidney tissue. Based on the study results, formalin and Bouin were more suitable for heart and cartilage tissue. Considering that in the histopathological evaluation both the cytoplasm and the nucleus are evaluated, it is suggested to choose the fixative suitable for the type of tissue.

Sinapic acid attenuates cyclophosphamide-induced liver toxicity in mice by modulating oxidative stress, NF-κB, and caspase-3.

Objectives: Cyclophosphamide (CP) as an antineoplastic drug is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA) as a natural phenylpropanoid has anti-oxidant, anti-inflammatory, and anti-cancer properties. Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked. Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation, and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.