Evaluation of the Therapeutic Effect of the Traditional Herbal Medicine Atrifil and Oshagh Gum on Testosterone-Induced Benign Prostatic Hyperplasia in Wistar Rats.

Benign prostatic hyperplasia (BPH) is a common disease that affects elderly men with various complications. This study evaluates the effects of an Iranian traditional herbal medicine "Atrifil and Oshagh gum" on BPH in male Wistar rats. Atrifil is a combination of three medicinal plants: Emblica officinalis Gaertn, Terminalia chebula Retz, and Terminalia bellerica Retz" extracts, and Oshagh gum is Dorema ammoniacum D. Dono gum. In this study, 30 male Wistar rats were divided into five groups: normal control, disease, finasteride, and extract with 300 and 600 mg/kg groups. The extract is a combination of hydroalcoholic Atrifil extract and Oshagh gum. All groups received intramuscular testosterone enanthate to induce BPH except the normal control group. On the twenty-eighth day, prostate glands were separated. Histopathological changes were observed. Furthermore, the prostate-specific antigen (PSA) and prostate weights were measured. The binding propensities of finasteride, equol, and flavonoids present in this extract such as quercetin, rutin, and kaempferol for 5α-reductase, estrogen receptor alpha and beta, and estrogen-related receptor gamma were assessed using in silico docking approach. Histopathological evaluation, biochemical parameter, and PSA level results indicated significant inhibition of accruing and progression of BPH in groups treated with 600 mg/kg extract (p < 0.01). Furthermore, molecular docking showed that rutin had a high affinity to bind the receptors 5α-reductase, estrogen receptor beta, and estrogen-related receptor gamma even more than finasteride, and on average, quercetin had a higher affinity to all these receptors. In the end, it can be concluded that Atrifil and Oshagh gum is effective in preventing BPH.

A Comprehensive Review on the Ethnopharmacology, Phytochemistry, Pharmacology, and Toxicology of the Mandragora Genus; from Folk Medicine to Modern Medicine.

The Mandragora genus (Solanaceae) is well known for its association with myths and has been used in herbal medicine since ancient times. This extensive literature review synthesizes the information currently available on the ethnobotany, Persian medicine (PM), traditional use, phytochemistry, pharmacology, and toxicity profile of Mandragora spp. The electronic search engines Scopus, Web of Science, PubMed, Google Scholar, and ScienceDirect were searched using keywords such as Mandragora, mandrake, phytochemistry, ethnopharmacology, Persian medicine, ethnobotany, and toxicity. Pertinent information was also extracted from books on PM, ethnomedicine, and dissertations. Mandragora species are found throughout the Mediterranean basin, Europe, Northern Africa, and the Himalayan regions. Traditionally, the species have been used to treat insomnia, dysuria, hemorrhoids, rheumatic pain, toothache, melancholia, and depression, among many others. In vitro studies have confirmed the biological properties of Mandragora spp. crude extracts, such as antioxidant, immunomodulatory, and enzyme-inhibiting effects. Various phytochemicals, such as alkaloids (e.g., atropine and scopolamine), coumarins (e.g., umbelliferone and scopoletin), withanolides (e.g., salpichrolide C), and lipid-like compounds (e.g., beta-sitosterol), have been isolated from Mandragora spp. Some of the pure compounds composing this plant are highlighted for their biologically active effects, including anticholinergic, antidepressant, antioxidant, and anti-inflammatory effects. Modern identifications of biological activities of the compounds isolated from Mandragora, especially alkaloids, support its traditional uses (e.g., for their narcotic effects). More in vivo studies are required to further understanding and most effectively utilize this genus, and extensive toxicological studies are required to validate its safety in clinical use.

Promising In Vitro Anti-Toxoplasma gondii Effects of Commercial Chitosan.

CDATA[Background: Toxoplasmosis is a disease that results from infection with an obligate intracellular T. gondii parasite, one of the world's most common parasites. Considering the complications of chemical drugs and the need for an appropriate drug combination for treatment of toxoplasmosis and considering the antimicrobial potential of chitosan, as a natural source, this study was aimed to evaluate in vitro activity of commercial chitosan (CC) on T. gondii. METHODS: In this experimental study, the tachyzoites of T. gondii were collected from the peritoneal exudates from infected Balb/c mice. The tachyzoites were diluted in phosphate buffer saline (PBS) solution. Chitosan with low molecular weight was commercially purchased. Then, at concentrations of 10, 50, 100, and 200 µg/mL and after 30, 60, 120, and 180 minutes, the viability of tachyzoites was determined by using trypan blue 0.1%. Anti-T.gondii activity of CC in all concentrations was significantly higher than pyrimethamine as the control group (P=0.05). RESULTS: The concentration of 200 µg/mL of CC had the highest effects and killed 30.5, 52, 59, and 81.5% of tachyzoites after 30, 60, 120, and 180 minutes. Moreover, IC50 values of CC were 515, 171, 12.5, and <10 µg/mL in comparison with pyrimethamine as 58.82 µg/mL for 30, 60, 120, and 180 min of exposure time. CONCLUSION: Our results indicate that chitosan in low molecular weight had potent activity against T. gondii tachyzoites and could be an appropriate candidate for the treatment of at least acute toxoplasmosis, certainly, after complementary in vivo experiments.

Naringin and naringenin as anticancer agents and adjuvants in cancer combination therapy: Efficacy and molecular mechanisms of action, a comprehensive narrative review.

Although the rates of many cancers are controlled in Western countries, those of some cancers, such as lung, breast, and colorectal cancer are currently increasing in many low- and middle-income countries due to increases in risk factors caused by development and societal problems. Additionally, endogenous factors, such as inherited mutations, steroid hormones, insulin, and insulin-like growth factor systems, inflammation, oxidative stress, and exogenous factors (including tobacco, alcohol, infectious agents, and radiation), are believed to compromise cell functions and lead to carcinogenesis. Chemotherapy, surgery, radiation therapy, hormone therapy, and targeted therapies are some examples of the approaches used for cancer treatment. However, various short- and long-term side effects can also considerably impact patient prognosis based on clinical factors associated with treatments. Recently, increasing numbers of studies have been conducted to identify novel therapeutic agents from natural products, among which plant-derived bioactive compounds have been increasingly studied. Naringin (NG) and its aglycone naringenin (NGE) are abundantly present in citrus fruits, such as grapefruits and oranges. Their anti-carcinogenic activities have been shown to be exerted through several cell signal transduction pathways. Recently, different pharmacological strategies based on combination therapy, involving NG and NGE with the current anti-cancer agents have shown prodigious synergistic effects when compared to monotherapy. Besides, NG and NGE have been reported to overcome multidrug resistance, resulting from different defensive mechanisms in cancer, which is one of the major obstacles of clinical treatment. Thus, we comprehensively reviewed the inhibitory effects of NG and NGE on several types of cancers through different signal transduction pathways, the roles on sensitizing with the current anticancer medicines, and the efficacy of the cancer combination therapy.

In Vitro Antiprotozoal Effects of Nano-chitosan on Plasmodium falciparum, Giardia lamblia and Trichomonas vaginalis.

BACKGROUND: Treatment of parasitic infections with conventional drugs is associated with high toxicity, and undesirable side effects require cogent substitutions. Nanotechnology has provided novel approaches to synthesize nano-drugs to improve efficient antipathetic treatment. PURPOSE: Nano-chitosan as a nontoxic antimicrobial agent was examined against three most prevalent protozoa in humans, Plasmodium falciparum, Giardia lamblia and Trichomonas vaginalis. METHODS: Chitosan extracted from Penicillium fungi was converted to nanoparticles to maximize its therapeutic properties. Safety of nano-chitosan was examined by determining its hemolytic property and toxicity on PC12 cells. The studied parasites were identified with RFLP-PCR and cultivation in relevant media. Characteristics of nano-chitosan as an useful and valuable curative compound was evaluated by FTIR, DLS and SEM. Dose dependent anti-parasitic effect of nano-chitosan was evaluated. RESULTS: The highest anti-parasitic activity of the nano-chitosan was observed at 50 µg/mL by which growth rates of cultivated P. falciparum, T. vaginalis and G. lamblia were inhibited by 59.5%, 99.4%, and 31.3%, respectively. The study demonstrated that nano-chitosan with the least toxicity, low side effects, and substantial efficacy deserved to be considered as an anti-parasitic nano-compound. CONCLUSION: Nano-chitosan significantly inhibited protozoan growth in vitro promising to explore its use to combat parasitic infections. Further investigations covering extended sample size, in vivo experiments and optimizing the concentration used may lead to efficient treatment of protozoan diseases.

Utilization of the Parenteral Morphine in Emergency Department using the Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) System.

OBJECTIVE: To evaluate the utilization of the parenteral morphine in Emergency Department (ED) using the Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) system. METHODS: In this retrospective cross-sectional study, morphine administration was recorded in 4-year time period from January 2013 to December 2016 in the ED of a referral center. The dose of the administered morphine was evaluated using the ATC/DDD system. The ATC/DDD of the parenteral morphine was calculated based on the world health organization (WHO). The data was evaluated based on the different diagnosis and conditions using the ATC/DDD protocol. RESULTS: In this study, 500 patients referred to ED with mean age of 48.29 ± 10.10 years were included. There were 306 (61.2%) men and 194 (38.8%) women among the patients. The lowest and highest DDD of parenteral morphine were 0.1 and 0.43, respectively. The utilization of parenteral morphine was significantly higher in men when compared to women (p<0.001). Those with history of tricyclic anti-depressant (TCA) consumption (p<0.001) and opium addiction (p<0.001) had significantly higher parenteral morphine utilization. Those with pain in the extremities and chest pain had significantly higher parenteral morphine utilization (p<0.001). CONCLUSION: The utilization of parenteral morphine in the ED of our center was higher than the WHO standard dosage. The morphine utilization was associated with male gender, opium addiction and TCA consumption.

Pulmonoprotective Action of Zataria multiflora Ethanolic Extract on Cyclophosphamide-Induced Oxidative Lung Toxicity in Mice.

OBJECTIVE: To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice. METHODS: Mice were intraperitoneally pre-treated with various doses of Zataria multiflora extract (50, 100, 200, and 400 mg/kg) once daily for 7 consecutive days. Animals were then injected with a single 200 mg/kg intraperitoneal dose of CP 1 h after the last administration of O. vulgare. Twenty-four hours later, mice were euthanized, the lungs were immediately removed, and biochemical and histological studies were conducted. RESULTS: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with Zataria multiflora significantly inhibited the elevation of lipid peroxidation level and the depletion in glutathione content, and superoxide dismutase and catalase activities induced by CP in lung. In addition, Zataria multiflora effectively alleviated CP-induced histopathological abnormality and pulmonary damages in mice lung tissues. CONCLUSIONS: The results reveal that Zataria multiflora protects lung tissues from CP-induced toxicity and suggest a role for oxidative stress in the pathogenesis of lung toxicity produced by CP in mice. Because Zataria multiflora has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a good supplement for reducing organ toxicity in patients undergoing chemotherapy, besides their consolidated ethnopharmacological uses.

Effects of some natural products from fungal and herbal sources on Giardia lamblia in vivo.

Giardia lamblia (G. lamblia) is the most widely known protozoan parasite that causes human gastrointestinal infection worldwide. Some natural compounds exhibited pivotal effects against different infectious diseases. In this research, the antigiardial activity and cytotoxicity of fungal chitosan, nano-chitosan, Rhamnus cathartica (R. cathartica) and emodin were evaluated in Balb/c mice. Genotyping of G. lamblia was assessed by PCR-RFLP technique. Different concentrations of mentioned compounds were used to check their antigiardial and cytotoxicity effects on human intestinal epithelial cells (HT-29) after 24, 48 and 72 h. The G. lamblia strain used in the current work was genotyped and revealed as an AII assemblage. All the concentration showed acceptable activity against G. lamblia cysts and trophozoites in comparison to the negative and positive controls (furazolidone and metronidazole) in vitro (P 0.05). The maximum mortality rate (100%) was achieved at 100 and 50 µg kg-1 concentrations after 48 and 72 h of exposure time, respectively. Our results provide significant information about the new antigiardial agent and proposed the nano-chitosan and emodin for the development of new drugs against G. lamblia in the future.

Ethnopharmacology of Cuscuta epithymum: A comprehensive review on ethnobotany, phytochemistry, pharmacology and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta epithymum (L.) L. (C. epithymum; Convolvulaceae) is a parasitic plant that has long been used locally and traditionally in Asia, Europe and other regions. AIM OF THE REVIEW: The study intends to reflect the significance of the C. epithymum in traditional medicine. This review aims to grant insight into the species' botany, pharmacological activities and phytochemistry with distinctive emphasis on its ethnomedicinal and traditional applications in all over the world. The review endeavors to rule out any inconsistency between the species' traditional application and its pharmacological activity, and presenting any coherence existing. MATERIALS AND METHODS: The books on ethnomedicine and the main medieval Persian medicine textbooks including Makhzan Al- Advieh, The canon of medicine, Zakhireh kharazmshahi and etc were explored for C. epithymum. Additionally, information on the ethnobotany, phytochemistry, morphology, taxonomy, modern medicinal uses, and pharmacological activities were collected in electronic databases including Google Scholar, Science Direct, Scopus, and PubMed using the keywords "Cuscuta epithymum," "traditional medicine," "ethnomedicine," "phytochemistry," "pharmacology" and "activity." Then, the available articles from 1975 to 2017 were employed for this study. RESULTS: C. epithymum is a rootless plant, widely distributed and available in every continent except Antarctica. It was used traditionally in formularies or by rural people and as geriatric drug, detergent, purgative, disorders in the melancholic humor, joint, kidney, urinary tract, gastrointestinal system, nervous system, etc. In modern medicine, the extract of C. epithymum showed anti-microbial, cytotoxic, anticonvulsant, anti-urease, immune stimulatory, hepatoprotective effect, and antioxidant activity. The main phytochemical constituents are alkaloids; saponins; tannins; triterpenoids; steroids; carbohydrates; aromatic compounds; flavonoids and the hydroxycinnamic acid derivatives. CONCLUSION: The modern pharmacological studies have validated the traditional and ethnobotanical uses of C. epithymum. However, many aspects of this herb have not been studied yet. In addition, information about the phytochemistry and toxicological profile is insufficient. Owing to the extensive traditional uses of C. epithymum. Hence further studies on pharmacological activities, phytochemistry, and toxicity and adverse effects seem to be necessary to appraise the medicinal values of C. epithymum.

Formulation and Evaluation of Licorice Shampoo in Comparison with Commercial Shampoo.

AIM: Glycyrrhiza glabra (G. glabra) or licorice with isoflavonoid, flavonoids, and triterpenoid glycosides (saponins) components are highly regarded in the cosmetic industry. This study has been planned as the first project for formulating a new herbal shampoo by utilizing the aqueous extracts of G. glabra. MATERIALS AND METHODS: The dried powdered root of G. glabra was extracted with boiled water through percolation method, and the pH was set by ammonia; then it was used with other constituents to formulate the herbal shampoo. The desirability of licorice shampoo was evaluated by physicochemical tests including visual inspection, detergency evaluation, pH assessment, percentage of solid contents, viscosity, foaming volume, and wetting time and compared with a commercial shampoo. Also, the product was checked for microbial control and consumers were asked about the quality of the licorice shampoo. RESULTS: The licorice shampoo has excellent cleansing ability, acceptable clarity, and viscosity. The volume of created foam and the wetting time were similar to the commercial shampoo. No microbial contamination was observed during the microbial control assessment tests. The licorice shampoo scored well on consumer's poll and was free from complication and also able to obviate hair and scalp problems. DISCUSSION AND CONCLUSION: The results indicated that the consumers were satisfied with using the formulated licorice shampoo. Licorice shampoo seems to be helpful in obviation of hair problems, but specific investigations are required to prove this claim. The shampoo was safe from microbial contamination and showed acceptable results in physicochemical evaluations. Licorice shampoo could be useful in the treatment of many hair diseases, so further research is needed for discovering the potential of licorice shampoo.

Comparison of Albizia Julibressin and Silver Sulfadiazine in Healing of Second and Third Degree Burns.

BACKGROUND: Large numbers of population suffer from burn annually. The promising treatment of burn has not been identified yet. Albizia julibressin (A. julibressin) in Fabaceae family is popular for its antiseptic activity. This prospective study was designed to compare the wound healing effects of A. julibressin gel (AG) with silver sulfadiazine (SSD). METHODS: This single blind clinical trial was performed on 40 patients with second and third degree burns. 20 patients treated with SSD and 20 other patients received A. julibressin. The percentage of the wound healing was evaluated with pain, irritation, edema, itching, erythema, purulent discharges and skin discoloration symptoms. Also, the patients' satisfaction and adverse drug reactions were determined. RESULTS: The severity of pain (p=0.03), inflammation (p=0.02) and purulent secretions (p=0.03) were significantly relieved in A. julibressin group. The healing time significantly reduced in second degree burns (p=0.03) and third degree burns (p=0.04) with treating by A. julibressin. No significant adverse drug reactions were detected with A. julibressin. CONCLUSION: It seems that A. julibressin improves the different therapeutic aspects of burn injuries and could be considered as a new herbal remedy in wound healings.

Ability of Ultrasonography in Detection of Different Extremity Bone Fractures; a Case Series Study.

INTRODUCTION: Despite radiography being the gold standard in evaluation of orthopedic injuries, using bedside ultrasonography has several potential supremacies such as avoiding exposure to ionizing radiation, availability in pre-hospital settings, being extensively accessible, and ability to be used on the bedside. The aim of the present study is to evaluate the diagnostic accuracy of ultrasonography in detection of extremity bone fractures. METHODS: This study is a case series study, which was prospectively conducted on multiple blunt trauma patients, who were 18 years old or older, had stable hemodynamic, Glasgow coma scale 15, and signs or symptoms of a possible extremity bone fracture. After initial assessment, ultrasonography of suspected bones was performed by a trained emergency medicine resident and prevalence of true positive and false negative findings were calculated compared to plain radiology. RESULTS: 108 patients with the mean age of 44.6 ± 20.4 years were studied (67.6% male). Analysis was done on 158 sites of fracture, which were confirmed with plain radiography. 91 (57.6%) cases were suspected to have upper extremity fracture(s) and 67 (42.4%) to have lower ones. The most frequent site of injuries were forearm (36.7%) in upper limbs and leg (27.8%) in lower limbs. Prevalence of true positive and false negative cases for fractures detected by ultrasonography were 59 (64.8%) and 32 (35.52%) for upper and 49 (73.1%) and 18 (26.9%) for lower extremities, respectively. In addition, prevalence of true positive and false negative detected cases for intra-articular fractures were 24 (48%) and 26 (52%), respectively. CONCLUSION: The present study shows the moderate sensitivity (68.3%) of ultrasonography in detection of different extremity bone fractures. Ultrasonography showed the best sensitivity in detection of femur (100%) and humerus (76.2%) fractures, respectively. It had low sensitivity in detection of in intra-articular fractures.

The anti-giardial effectiveness of fungal and commercial chitosan against Giardia intestinalis cysts in vitro.

Chitosan with poly-N-acetylglucosamine sequences is a deacetylated derivative of chitin that can be found in the exoskeletons of crabs, shrimp and lobsters, the cuticles of insects and the cell walls of fungi. The aim of the present study was to compare the effects of fungal chitosan (FC) prepared from the cell walls of Penicillium viridicatum and Penicillium aurantiogriseum with commercially available chitosan (CC) against Giardia intestinalis cysts in vitro. The giardia cysts were isolated using a sucrose method. Four concentrations (50, 100, 200 and 400 µg/ml) of each type of prepared chitosan were applied for 10, 30, 60 and 180 min. The viability of the cysts was checked via 0.1 % eosin staining. Our results indicate that P. viridicatum (with a 47.5 % DD) and P. aurantiogriseum (with a 47.3 % DD) at different concentrations after 180 min precipitated, respectively, 56, 69, 81 and 100 %, and 63, 75, 86 and 100 % mortality rates. CC (with a 54 % DD) showed 79, 84, 93 and 100 % mortality rates. In conclusion, both FC and CC at 400 µg/ml concentrations after 180 min of exposure showed the most potent effect against G. intestinalis cysts. Accordingly, chitosan could be suggested as a new natural nanoform agent for future research in the safe and effective treatment of Giardia infections.

Drug use evaluation of Meropenem at a tertiary care university hospital: A report from Northern Iran.

OBJECTIVE: The inappropriate use of antibiotics remains the primary factor in antimicrobial drug resistance. In this study, we evaluate the use of meropenem in surgical/medical wards of Imam Khomeini Tertiary Referral Hospital, Sari, Iran. METHODS: This retrospective observational study was used to assess rational use of meropenem. The study was conducted by reviewing medical records of 100 admitted patients who received meropenem during March 2013 to January 2014. FINDINGS: Meropenem was prescribed most frequently in Intensive Care Unit (22%), and pneumonia was the most common diagnosis (35%). The third-generation cephalosporins were the most frequently prescribed antimicrobials after meropenem (53%). In 21% of the patients, imipenem was changed to meropenem. Most of the inappropriate uses were seen in terms of frequency of meropenem use (34%), followed by duration of meropenem therapy (28%). CONCLUSION: Comparing our study results has shown higher inappropriate use. It is necessary to take action to improve prescribing habit in order to reduce the unnecessary usage of antibiotic thus enhance rational antibiotic use.

In vitro protoscolicidal effects of fungal chitosan isolated from Penicillium waksmanii and Penicillium citrinum.

Hydatidosis is caused by a tapeworm which infects humans by the larval stage. In humans, the disease is so serious that it requires surgery for treatment. Documents show that there have been many efforts in finding new scolicidal agents for reducing the rate of the infection. The objective of this study was determination of the scolicidal effect of two fungal chitosan types, produced from Penicillium spp. and commercially chitosan (CC) on Echinococcus granulosus protoscolex. Protoscolices were aseptically aspirated from sheep livers hydatid cysts. Four concentrations (50, 100, 200, 400 µg/ml) of each type of prepared chitosan were used for 10, 30, 60 and 180 min. Viability of protoscolices was detected by 0.1 % eosin staining. Fungal chitosan which was the most bioactive type with higher degree of deacetylation showed stronger scolicidal activity in vitro (P < 0.05). Fungal chitosan could be recommended, as good as CC for hydatid cysts control and is a noble alternative for synthetic and chemical scolicidal.

Genoprotective effects of Origanum vulgare ethanolic extract against cyclophosphamide-induced genotoxicity in mouse bone marrow cells.

CONTEXT: Cyclophosphamide (CP), an alkylating chemotherapeutic agent, can bind DNA, causing chromosome breaks, micronucleus (Mn) formation, and cell death. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against DNA damage. OBJECTIVE: The genoprotective effect of O. vulgare ethanolic extract against CP-induced genotoxicity in mouse bone marrow cells was evaluated using a Mn assay. MATERIALS AND METHODS: Mice were pre-treated with aerial parts of O. vulgare ethanolic extract at different doses (50, 100, 200, or 400 mg/kg) for 7 d. One hour after the last administration of O. vulgare, animals were injected with CP at 200 mg/kg. After 24 h, the bone marrow cells of both femurs were flushed and the frequency of MnPCEs was evaluated to measure the chromosomal damages. In addition, the number of PCEs per 1000 NCEs in each animal was recorded to evaluate the bone-marrow suppression; mitotic activity was calculated as [PCE/(PCE + NCE)] × 100 to assess the cell division. RESULTS: At 400 mg/kg, O. vulgare displayed its maximum protective effect, reduced the number of MnPCEs from 10.52 ± 1.07 for CP group to 2.17 ± 0.26 and completely normalized the mitotic activity (p < 0.001). Origanum vulgare also led to significant proliferation and hypercellularity of immature myeloid elements after the mice were treated with CP, mitigating the bone marrow suppression. DISCUSSION AND CONCLUSION: Origanum vulgare ethanolic extract exerts a potent genoprotective effect against CP-induced genotoxicity in mice bone marrow, which might be possibly due to the scavenging of free radicals during oxidative stress conditions.

Protective effects of Origanum vulgare ethanol extract against cyclophosphamide-induced liver toxicity in mice.

UNLABELLED: Abstract Context: Despite its wide clinical use, cyclophosphamide (CP), an alkylating chemotherapeutic agent, possesses many adverse effects, including hepatotoxicity. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against above-mentioned damage. OBJECTIVE: This study evaluated the protective effects of O. vulgare extract on CP-induced liver toxicity. MATERIALS AND METHODS: Mice were pretreated with aerial parts of O. vulgare ethanolic extract (intraperitoneally) at doses of 50, 100, 200, and 400 mg/kg for 7 consecutive days before the administration of a single 200 mg/kg intraperitoneal dose of CP 1 h after the last injection of O. vulgare. After 24 h, animals were anesthetized, blood samples and hepatic tissues were collected and used for biochemical and histological examination. RESULTS: Serum levels of hepatic markers were increased after CP treatment but restored in the O. vulgare-pretreated groups. The serum ALT, AST, and ALP of the CP group were 196.49 ± 3.82, 143.78 ± 4.79, and 203.18 ± 3.81 IU/l, respectively. However, pretreatment with 400 mg/kg O. vulgare significantly decreased the serum ALT, AST, and ALP to 52.49 ± 2.18, 44.78 ± 2.06, and 65.62 ± 1.73 IU/l, respectively (p < 0.001). Histological examinations also confirmed the protective effects of O. vulgare against CP-induced liver toxicity. DISCUSSION AND CONCLUSION: Our results reveal that O. vulgare with high amount of flavonoids and phenolic compounds induces potent hepatoprotective mechanisms against CP. Therefore, O. vulgare might help defend the body against the side effects, particularly hepatic damages induced by chemotherapeutic agents.

Prophylactic efficacy of melatonin on cyclophosphamide-induced liver toxicity in mice.

The current study aimed to evaluate the protective effects of melatonin, a pineal secretory product, against hepatotoxicity induced by cyclophosphamide (CP) in mice. Mice were pretreated with melatonin intraperitoneally for 7 consecutive days before the administration of a single intraperitoneal dose of 200 mg/kg CP. 24 hr after CP administration, the mice were anesthetized, blood was then removed, and serum toxicity enzymes activities were evaluated. After the blood sampling, all animals were killed, livers were then removed, and histological studies were conducted. Serum toxicity marker enzymes were significantly increased after CP treatment but restored in melatonin pretreated groups. In addition, administration of CP induced necrotic hepatocyte with small crushed nuclei, portal space with severe inflammation, and hepatocytes surrounded by lymphocytic infiltration in hepatic tissues. However, melatonin effectively protected against CP-induced histopathological abnormalities in the liver tissues. Our results reveal that melatonin produces a potent hepatoprotective mechanism against CP. Therefore, melatonin could be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity of CP for the patients undergoing chemotherapy.