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Zoledronic acid (ZLD) is a bisphosphonate drug widely administered against pathological conditions such as hypercalcemia of malignancy, osteoporosis, bone metastases from solid tumors, and multiple myeloma. Unfortunately, renal injury is a serious and dose-limiting adverse effect of ZLD. There is no specific mechanism for ZLD-induced renal damage. The current study aimed to assess the effects of ZLD (10 and 15 mg/kg, i.p., single dose) on the rat kidney. In this regard, several parameters, including oxidative stress biomarkers, serum level of BUN and creatinine, inflammatory cytokines, kidney histopathology, and indices of mitochondrial function were assessed. A significant increase in serum Cr and BUN revealed renal injury. Moreover, kidney histopathological changes, including interstitial inflammation, tissue necrosis, and tubular atrophy, were detected in ZLD-treated rats. Biomarkers of oxidative stress, including a significant increase in reactive oxygen species (ROS), depletion of kidney glutathione (GSH) stores, increased lipid peroxidation, and suppression of the total antioxidant capacity, were detected in ZLD-treated animals. ZLD also significantly increased renal levels of TNF-α, IL-6, and IL-1β. ZLD exposure was also associated with significantly decreased mitochondrial dehydrogenases activity, mitochondrial depolarization, mitochondrial permeabilization, and ATP depletion. These data highlight mitochondrial dysfunction, inflammatory response, and oxidative stress as potential mechanisms in ZLD-induced kidney injury.

Insulitis is the inflammation of beta cells of the Langerhans islets. It is well-known that insulitis is a prevalent complication of diabetes. A series of xenobiotics, including drugs, could also induce insulitis. The current study evaluated the effect of zoledronic acid (ZLD) on the pancreas in an animal model. Actually, in an attempt to evaluate the adverse effects of ZLD on the kidney, we noticed severe morphological alterations in the pancreas. Therefore, the effects of ZLD on the pancreas tissue were further investigated. Rats received ZLD (10 and 15 mg/kg, single dose, i.p) and pancreas weight index, serum biomarkers of pancreas injury, the level of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), oxidative stress biomarkers in this organ, and pancreas histopathological alterations were assessed. A significant increase in pancreas weight index was detected in ZLD-treated animals. ZLD also significantly increased serum amylase and lipase levels. No significant changes in serum glucose were detected in this study. A significant increase in reactive oxygen species, lipid peroxidation, decreased glutathione levels, and antioxidant capacity was also evident in the pancreas of ZLD-treated rats. Histopathological findings indicate the insulitis lesions of the islets of Langerhans at both doses of 10 and 15 mg/kg of ZLD. The data obtained from this study revealed insulitis as a serious adverse effect associated with high doses of ZLD. Clearly, further studies are warranted to evaluate the effects of other doses and/or patterns of administration of ZLD on pancreas tissue and, finally, the clinical significance of these data.

Cyclophosphamide is one of the most prescribed antineoplastic agents. Hemorrhagic cystitis is one of the most common side effects of cyclophosphamide. Captopril is usually used as an anti-blood pressure agent. On the other hand, as a thiol group-containing agent, captopril has potent antioxidant activity. This study aims to evaluate the effect of captopril on cyclophosphamide-induced hemorrhagic cystitis in rats. Twenty-five male Sprague-Dawley rats were equally divided into five groups. Group I received saline (10 ml/kg, i.p.), Group II received a single dose of Cyclophosphamide (200 mg/kg, i.p), Groups III-V received cyclophosphamide and mesna (40 mg/kg, i.p.) or captopril (20 and 40 mg/kg, i.p.). Histopathological changes of bladder, liver, and kidney and lipid peroxidation and glutathione contents in the kidney and liver were monitored. Moreover, serum markers of organ injury were measured. It was found that captopril (20 and 40 mg/kg, i.p) and mesna (40 mg/kg, i.p), as the standard treatment of cyclophosphamide-induced hemorrhagic cystitis, conspicuously attenuated the macroscopic and microscopic damage in the bladder induced by cyclophosphamide. In contrast, mesna did not significantly improve histopathological changes. No significant difference in the serum level of liver and kidney injury biomarkers, tissue biomarkers of oxidative stress, and histopathological alteration were detected between control and cyclophosphamide-treated animals. On the other hand, both captopril and mesna alleviated histopathological bladder changes. Although the mechanism of action of captopril seems not to be mediated by alleviating oxidative stress, the present study results indicate that this drug could have a protective effect on cyclophosphamide-induced hemorrhagic cystitis.

Cirrhosis-associated muscle mass loss or sarcopenia is a common complication (17-30% prevalence) in cirrhotic patients. However, the pathogenesis of this complication is poorly understood. Therefore, finding the mechanisms of sarcopenia could lead to the development of therapeutic strategies against this complication. In the current study, rats underwent bile duct ligation (BDL) surgery, and their skeletal muscle (gastrocnemius; GS) was isolated and assessed 28 and 56 days after BDL operation. Significant increase in biomarkers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, and increased oxidized glutathione (GSSG) levels were detected in the muscle of cirrhotic animals. Skeletal muscle tissue antioxidant capacity and reduced glutathione (GSH) were also significantly decreased in BDL rats. Moreover, deterioration of several mitochondrial indices, including mitochondrial depolarization, increased mitochondrial permeabilization, depleted ATP reservoirs, and decreased mitochondrial dehydrogenases activity, were evident in the GS isolated from cirrhotic rats. Based on these data, oxidative stress and mitochondrial impairment seem to play as primary mechanisms of cirrhosis-induced sarcopenia.

Solenanthus circinatus root, commonly called “Azaar Choob” in Persian medicine, has a very long history of use in relieving pain and inflammation in muscle contusion and bone bruises and fractures. In this study, the analgesic effect of root extract and various fractions of S. circinatus were assessed in male rats using tail flick and formalin tests. Powdered roots of the plant was extracted with ethanol in a soxhlet apparatus and then fractionated with solvents of increasing polarity including petroleum ether, chloroform, ethyl acetate and n-butanol in a liquid-liquid extractor. Ethanolic extract and fractions were then chromatographed on silica gel TLC plates using various solvent systems. The spots on the chromatograms visualized using colour reagents which showed the presence of various compounds. In order to evaluate analgesic effect, rats were treated with 200 mg/kg of extract and fractions intraperitoneally and verified by tail-flick and formalin tests and compared with diclofenac group (25 mg/kg) as a standard drug. Extract and almost all fractions revealed significant analgesic effects compared to the control group. Based on the results, analgesic activity of root extract and fractions of S. circinatus were comparable with that of diclofenac. Petroleum ether fraction displayed higher pain relieving activity than diclofenac at 25 mg/kg in tail-flick test. Interestingly the analgesic efficacy of petroleum ether fraction surpassed other fractions at 60 min interval after injection. Ethyl acetate and petroleum ether were found to be superior to other fractions in manifestation of analgesic activity. The root extract is currently under further detailed investigation.

Taurine (TAU) is the most abundant free amino acid in the human body. High concentrations of this amino acid are found in tissues such as the skeletal muscle, brain, and kidney. Recently, a focus has emerged on the effects of TAU on cellular mitochondria. It has been found that TAU could positively affect this organelle by enhancing mitochondrial membrane potential, increasing ATP levels, and mitigating mitochondria-mediated ROS formation. The current study aimed to evaluate the effect of a wide range of TAU concentrations (0.01 mM-1000 mM) on mitochondrial function. Mice liver mitochondria were isolated and exposed to different concentrations of TAU (30 min). Several indices, including mitochondrial depolarization, dehydrogenases activity, permeabilization, and ATP content, were monitored. It was found that TAU supplementation significantly enhanced parameters such as mitochondrial ATP levels and mitochondrial membrane potential in comparison with the control group. Moreover, TAU prevented Ca2+-induced mitochondrial permeabilization. This amino acid revealed no significant adverse effect on isolated mitochondria even at very high and supra-physiological concentrations (e.g., 100, 250, and 500 mM). These data suggest TAU as an ideal and safe agent to protect mitochondria against toxic insults or regulating cellular function in different mitochondria-linked disorders.

The present investigation was carried out to evaluate the pharmacognostic properties of Citrus aurantium seeds as well as its anti-inflammatory activities. The n-hexane fraction of seed oil extracted via a Soxhlet extractor and subjected to pharmacognostic assays, HPTLC and GC-MS analysis for determination of fatty acids and sterols. The possible anti-inflammatory and antinociceptive activities in rats were evaluated using formalin-induced paw licking, oedema and myeloperoxidase activity assessment. Total ash, acid insoluble and water soluble ash values were determined as 35.83 ± 4.92, 6.67 ± 2.89 and 28.33 ± 5.77 mg/g, respectively. HPTLC assessment revealed the presence of different fatty acids and steroidal triterpenes. The principal fatty acids of the seed oil were linoleic acid (C18:2, 50.10 ± 2.58 %) and Oleic acid (C18:1, 30.14 ± 0.39). Esterified (2.40 mg/g) and free β-sitosterol (32.90 mg/g), free campesterol (3.9 mg/g) and free stigmasterol (10.165 mg/g) were detected in the oil. Seed oil exhibited anti-inflammatory properties in the first and the second phases of formalin test. Also, it had anti-edematogenic effects but exerted no effects on myeloperoxidase activity.

The aim of this study was to evaluate the effect of the hexyl acrylate conjugated polyamidoamine (PAMSM) dendrimer on different cell lines in the presence and absence of serum. Although the positively charged dendrimers including PAMAM has been considered as efficient gene carriers, their cytotoxicity is a major barrier for their clinical applications. The conjugation of hexyl acrylate on PAMAM dendrimer was carried out to improve the hydrophilic-hydrophiobic balance of the dendrimer as well as the modulation of the positive charge on the dendrimer structure. The cytotoxicity of PAMAM derivatives was evaluated using MTT test on HepG2, MCF-7 and A549 cell lines in the presence and absence of serum. The results revealed that the modified PAMAM dendrimers induced less toxic effects on the cell lines in the presence of serum. Therefore, conjugation of acrylate on the PAMAM structure could be an efficient way to reduce the dendrimer toxicity allowing the administration of more dendrimer for gene delivery.

The liver is continuously exposed to a variety of xenobiotics. Several xenobiotics are identified which act as hepatotoxicants. Hence, finding protective agents for ameliorating xenobiotics-included liver injury has a great value. Eisenia foetida, a kind of “earthworm,” is a source of a wide range of bioactive components. Several investigations have been evaluated the E. foetida extract (EFX) for biomedical and nutritional applications. The current study was designed to evaluate the potential hepatoprotective properties of EFX in two experimental models of hepatic damage. Acetaminophen (APAP; 1 g/kg, i.p) was administered as the animal model of acute liver injury in mice. Bile duct ligated (BDL) rats were used as the animal model of chronic hepatic damage. Severe elevation in tissue biomarkers of oxidative stress including lipid peroxidation and hepatic glutathione depletion was evident in both APAP-treated and BDL animals. Moreover, serum biomarkers of liver injury were drastically increased in both acute and chronic animal models of hepatotoxicity. Significant liver tissue histopathological alterations including tissue necrosis, vascular congestion, and inflammatory cells infiltration were detected in APAP-treated and BDL animals. On the other hand, it was found that EFX supplementation (100, 200, 500, and 700 mg/kg, i.p) mitigated oxidative stress markers, decreased serum biomarkers of liver injury, and alleviated liver tissue histopathological changes. The hepatoprotection provided by EFX supplementation in the current study might be mediated through its potential antioxidative mechanisms.

Hepatic encephalopathy (HE) is a serious clinical complication, which could lead to coma and death if not appropriately managed. There is agreement on the predominant role of ammonia in the etiology of HE. Brain is one of the most critical organs affected by ammonia. The critical role of oxidative stress and its consequences in the pathogenesis of ammonia-induced brain injury have been revealed before. On the other hand, there is no promising therapeutic option against ammonia neurotoxicity. Taurine is one of the most abundant amino acids in the human body. Several pharmacological roles including brain protecting properties have been attributed to this amino acid. The current study was designed to evaluate the role of taurine supplementation on HE-induced oxidative stress in the brain tissue. Animals received thioacetamide (400 mg/kg, i.p, for three consecutive days at 24-hr intervals) as a model of acute liver failure and hyperammonemia. Several serum biochemical parameters, in addition to plasma and brain ammonia level, were monitored. Moreover, markers of oxidative stress in the brain of hyperammonemic animals were assessed. It was found that plasma and brain ammonia was increased, and serum markers of liver injury were significantly elevated in the thioacetamide-treated group. On the other hand, an increase in markers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, glutathione depletion, and decreased tissue antioxidant capacity, was detected in the brain tissue of thioacetamide-treated animals. It was found that taurine treatment (250, 500, and 1000 mg/kg, i.p) alleviated brain tissue markers of oxidative stress and decreased serum biomarkers of liver injury. Furthermore, lower plasma and brain ammonia were detected in taurine-treated animals. These data suggest taurine as a potential protective agent with therapeutic capability against HE-associated central nervous system complications.

Fulminant hepatic failure is a deleterious clinical complication, which leads to hyperammonemia. Ammonia is a noxious neurotoxic agent, which affects brain tissue through different mechanisms. On the other hand, it is well-known that oxidative stress and its consequences play a major role in the pathogenesis of ammonia-induced brain injury. Carnosine is a dipeptide abundantly found in the human central nervous system (CNS). This peptide is widely investigated for its neuroprotective properties. The current study aimed to evaluate the effect of carnosine supplementation on oxidative stress markers in the brain tissue of a rat model of fulminant hepatic failure and hyperammonemia. Animals received thioacetamide (400 mg/kg, i.p, for three consecutive days at 24-hr intervals) as a model of acute liver failure and hyperammonemia. Several serum biochemical parameters, in addition to plasma and brain ammonia level, were monitored. On the other hand, brain tissue markers of oxidative stress including reactive oxygen species (ROS) formation, lipid peroxidation, tissue glutathione content, and total antioxidant capacity were measured. It was found that plasma and brain ammonia was increased, and serum markers of liver injury were significantly elevated in the thioacetamide-treated group. On the other hand, an increase in markers of oxidative stress, including ROS formation, lipid peroxidation, glutathione depletion, and decreased tissue antioxidant capacity, was evident in the brain of thioacetamide-treated animals. It was found that carnosine supplementation (250, 500, and 1000 mg/kg) decreased serum markers of liver injury, mitigated brain, and plasma ammonia level, and alleviated brain tissue markers of oxidative stress. These data suggest carnosine as a potential neuroprotective agent with therapeutic capability against ammonia-induced CNS injury.

Recently use of antifungal drugs in human medicine has been increased, especially with the advent of AIDS epidemic. Despite the growing list of azoles, their clinical value has been limited by their relatively high risk of toxicity and the emergence of drug resistance. Efforts have focused on the development of new, less toxic and more efficacious antifungal agents. We previously described synthesis of some new azole derivatives. We also evaluated all the synthesized compounds for their antifungal activity. Most of our compounds showed desirable activity against different species of microorganisms. Here we choose thirteen of these compounds, 5 bentriazole derivatives (1a-5a), 5 imidazole derivatives (1b-5b) and 3 triazole derivatives (1c-3c) to evaluate their cytotoxic activities against a human cancer cell line (MCF-7) using colorimetric MTT cytotoxic assay. Their cytotoxic activities were compared to clotrimazole as a positive control. Our results collectively showed that most of our synthesized compounds had less cytotoxicity against MCF-7 compared to clotrimazole.

Valproic acid (VPA) is a widely administered drug against epilepsy and several other neurological disorders. On the other hand, liver injury is a deleterious side effect associated with VPA. Oxidative stress seems to play a critical role in VPA-induced hepatotoxicity. The current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithiothreitol (DTT) as thiol reducing agents have any protective effects against VPA-induced liver injury. Isolated rat hepatocytes (in vitro) were exposed to increasing concentrations of VPA (25, 50, 100, 150, and 250 µM) and markers of cytotoxicity were evaluated. Furthermore, animals received VPA (250 and 500 mg/kg, i.p for 15 consecutive days) (in vivo) and markers of liver injury were monitored. It was found that 250 µM of VPA caused marked cytotoxicity toward isolated hepatocytes as judged by trypan blue exclusion test. Moreover, markers of oxidative stress including glutathione depletion and lipid peroxidation were detected in VPA-treated hepatocytes. On the other hand, VPA caused a significant increase in plasma markers of hepatotoxicity in drug-treated group. Liver histopathological changes and markers of oxidative stress were also detected in VPA-treated animals. It was found that administration of NAC (1 mM), and DTT (1 mM) significantly alleviated VPA-induced cytotoxicity (In vitro). NAC (250 and 500 mg/kg) and DTT (15 and 30 mg/kg) also significantly mitigated VPA hepatotoxicity (In vivo). The data obtained from the current investigation indicate potential therapeutic properties of thiol reductants against VPA-induced liver injury.

The protective effects of Artemia salina L. extract was examined against carbon tetrachloride (CCl4)-induced cell toxicity. In the in vitro model of study, markers such as cell viability, cellular reduced and oxidized glutathione, and lipid peroxidation in HepG2 cells was evaluated. Human liver cancer cell line HepG2 was treated with CCl4 and Artemia salina extract, and markers of hepatotoxicity were investigated. Artemia salina extract showed significant dose-dependent protective effects against the cytotoxicity of CCl4. This extract was able to normalize the levels of GSH, and thiobarbituric acid-reactive (TBARs), which were altered due to CCl4 intoxication in HepG2 cells. As the oxidative stress markers were ameliorated, it might be concluded that Artemia salina extract possesses protective effects probably due to its antioxidant constituents.

Taurine (2-aminoethane sulfonic acid) is a non-protein amino acid found in high concentration in different tissues. Glycine (Amino acetic acid) is the simplest amino acid incorporated in the structure of proteins. Several investigations indicate the hepatoprotective properties of these amino acids. On the other hand, antineoplastic agents-induced serum transaminase elevation and liver injury is a clinical complication. The current investigation was designed to screen the possible hepatoprotective properties of taurine and glycine against antineoplastic drugs-induced hepatic injury in an ex vivo model of isolated perfused rat liver. Rat liver was perfused with different concentration (10 µM, 100 µM and 1000 µM) of antineoplastic drugs (Mitoxantrone, Cyclophosphamide, Cisplatin, 5‑Fluorouracil, Doxorubicin and Dacarbazine) via portal vein. Taurine and glycine were administered to drug-treated livers and liver perfusate samples were collected for biochemical measurements (ALT, LDH, AST, and K+). Markers of oxidative stress (reactive oxygen species formation, lipid peroxidation, total antioxidant capacity and glutathione) were also assessed in liver tissue. Antineoplastic drugs caused significant pathological changes in perfusate biochemistry. Furthermore, markers of oxidative stress were significantly elevated in drug‑treated livers. It was found that taurine (5 and 10 mM) and glycine (5 and 10 mM) administration significantly mitigated the biomarkers of liver injury and attenuated drug‑induced oxidative stress. Our data indicate that taurine and glycine supplementation might help as potential therapeutic options to encounter anticancer drugs-induced liver injury.

Platelet-rich plasma (PRP) is an attractive preparation in regenerative medicine due to its potential role in the healing process in different experimental models. This study was designed to investigate the wound healing activity of a new formulation of PRP. Different gel-based formulations of PRP were prepared. Open excision wounds were made on the back of male Sprague-Dawley rats, and PRP gel was administered topically once daily until the wounds healed completely (12 days). The results revealed that the tested PRP formulation significantly accelerated the wound healing process by increasing the wound contraction, tissue granulization, vascularization, and collagen regeneration. Interestingly, this study showed that there were no significant differences between the PRP and its gel-based formulation in all the above mentioned parameters. Although this investigation showed that PRP formulation had significant wound healing effects, the PRP gel-based formulation also had significant wound healing properties. This might indicate the wound healing properties of the PRP gel ingredients in the current investigation.

The cholestatic liver disease ensues with a hepatic accumulation of cytotoxic molecules. Several hydrophobic bile acids are known as cytotoxic agents accumulated in the liver during cholestasis. Chenodeoxycholic acid (CDCA) is a toxic hydrophobic bile acid. Oxidative stress and mitochondrial dysfunction are well-known mechanisms of bile acids cytotoxicity. In the current study, CDCA effect on isolated liver mitochondria was monitored by analyzing the changes in mitochondrial dehydrogenases activity, mitochondrial permeabilization, and mitochondrial membrane potential. On the other hand, taurine (1 mM) and carnosine (1 mM) were added as potential protective agents against CDCA-induced mitochondrial dysfunction. Increasing concentrations of CDCA (100 µM - 1000 µM) impaired mitochondrial membrane potential, decreased mitochondrial dehydrogenases activity and enhanced mitochondrial permeabilization and swelling. It was found that taurine and carnosine supplementation preserved mitochondrial function in the presence of CDCA. The results mention that toxicologically relevant concentrations of CDCA impaired mitochondrial function. On the other hand, taurine and carnosine might be applicable as protective agents against bile acids-induced mitochondrial impairment and toxicity.

Introduction: burn wounds are common happenings which cause many people have irreversible defects and to be death around the world every year. In this study, we evaluated the effects of Melilotus officinalis and Alpha ointment in the healing of burn wounds and compare their findings with silver sulfadiazine (SSD).Methods: Seventy-five male Sprague-Dawley rats were randomly divided into five groups, and similar burn ulcers were produced on the back of rats. The first group of rats received no treatment, base gel was used topically to group II, in groups III-V, Alpha, SSD and Melilotus officinalis preparations were applied, respectively. Wound healing, contraction and histopathological examination were evaluated at the end of 7, 14, and 21 days.Results: Alpha ointment was equally effective as Melilotus officinalis gel, while its efficacy was better compared to SSD for all parameters of wound healing on days 7, 14 and 21. Alpha and Melilotus officinalis preparations as less expensive medications which significantly improve the quality of wound healing and scar formation and also are more appropriate treatment choices than SSD.Conclusion: Alpha and Melilotus officinalis are recommended as alternative to SSD, especially in patients with low economical backgrounds or in those who show adverse reactions to SSD.

Carnosine is an abundantly found dipeptide present in different tissues. Several pharmacological properties have been attributed to carnosine. On the other hand, the precise mechanism of cytoprotection provided by carnosine remains obscure. The current study aimed to evaluate the direct effect of different concentrations of carnosine on cellular mitochondria as an essential target involved in the cytoprotection/cytotoxicity. Liver mitochondria were isolated and exposed to carnosine (0.01-20 mM). Mitochondrial depolarization, dehydrogenases activity, mitochondrial swelling and permeability, and ATP content were assessed. On the other hand, the effect of carnosine supplementation on calcium (Ca2+) overload-induced mitochondrial injury was evaluated. It was found that concentrations between 0.01-20 mM of this peptide preserved mitochondrial indices of functionality in a Ca2+ overloaded environment. These data represent regulation of mitochondrial function as a primary mechanism for the protective properties of carnosine.

Background: Cylophosphamide is used alone or in combinationwith other drugs for treatment of neoplastic diseases.Hemorrhagic cystitis is a major potential toxicity and doselimiting side effect of cyclophosphamide. The aim of thisstudy was to evaluate the effects of lycopene compared withsome antioxidants for the prevention of cyclophosphamideinduced hemorrhagic cystitis in rats.Methods: In this study, male Sparague-Dawley rats dividedinto 17 groups of six animals. Group 1 received saline (10ml/kg, i.p) as normal control, group 2 received cyclophosphamide(200 mg/kg, i.p) as a single dose, groups 3-10 receivedMesna (40 mg/kg, i.p), N-acetylcysteine (100 mg/kg i.p), dithiotheritol(50 mg/kg, i.p), L-carnitine (200 and 400 mg/kg,i.p), grape seed extract (500 mg/kg i.p) and lycopene (0.1 and0.5 mg/kg, i.p) alone. Groups 11-17 received Mesna (40 mg/kg,i.p), N-acetylcysteine (100 mg/kg, i.p), dithiotheritol (50 mg/kg,i.p), L-carnitine (400 mg/kg, i.p), grape seed extract (500mg/kg, i.p) and lycopene (0.1 and 0.5 mg/kg, i.p), 5 minutesbefore, and 2 and 6 hours after administration of 200 mg/kgcyclophosphamide. Pathological and biochemical analysis wasevaluated 24 hours after cyclophosphamide administration.Results: Mesna and N-acetylcysteine resulted in some but notfull protection against cyclophosphamide toxicity compared tothe controls. Lycopene (0.1 and 0.5 mg/kg) was efficient inprotecting the bladder from cyclophosphamide induced hemorrhagiccystitis. However, dithiotheritol, L- carnitine andgrape seed extract did not prevent hemorrhagic cystitis.Conclusion: Our results suggest that pre and co- treatment oflycopene (0.1 and 0.5 mg/kg) with cyclophosphamide mayhave therapeutic potential to inhibit the hemorrhagic cystitisby cyclophosphamide.

Background Anal fissure is a painful tear or crack in the distal part of anal canal. It usually involves the epithelium, but in the long term it may extend to the whole anal mucosa. Platelet Lysate (PL) hydrogel is a hemoderivitive pharmaceutical formulation that contains plenty of growth factors. These growth factors can induce tissue regeneration and revascularization as well as fibroblast proliferation. Objectives This study aimed to evaluate the effectiveness of PL hydrogel in the treatment of the anal fissure or retardation of its development. Patients and Methods The patients with chronic and acute anal fissure were randomly divided into groups of A and B. Group A received PL hydrogel and Rectol, while group B received placebo and Rectol. Then, they were followed and evaluated for two weeks. Results Although it was anticipated that platelet growth factors would be effective in anal fissure healing process, no significant difference was observed between the control group and the case group after the treatment. Nevertheless, a significant difference was observed within the two groups after the treatment. Conclusions PL hydrogel does not seem to have beneficial effects compared to the placebo or Rectol on the healing of anal fissure.