Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation.

The aim of this study was to investigate the molecular, biochemical, and histopathological effects of bromelain, which has antioxidant and anti-inflammatory properties, against cisplatin-induced ocular toxicity. The groups were designed as (1) Control, (2) Cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Bromelain (50 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Bromelain (100 mg/kg, orally for 14 consecutive days). The activity of total antioxidant capacity (TAC) and total oxidant status (TOS) and levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1ß (IL-1ß), IL-10, nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and 8-OHdG were measured in ocular tissue. The mRNA expression of NF-κB and Caspase-3 was also evaluated. Also, ocular sections were evaluated histopathologically. Bromelain demonstrated a dose-dependent protective effect in cisplatin-induced toxicity by regulating oxidative stress, inflammation, and tissue damage. Our results suggested that bromelain may be a potential adjuvant that can protect the eye from cisplatin-induced toxicity.

Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats.

This study was planned to assess the potential protective effects of taxifolin against thioacetamide-induced hepatic encephalopathy and subsequently to portray its behavioural results. The experimental model was induced with three doses of (200 mg/kg i.p.) thioacetamide and taxifolin (50 and 100 mg/kg, p.o.) was administered for fourteen days. Taxifolin effectively attenuated hepatic encephalopathy through decrease in AST, ALT, ALP and LDH concentrations and improvement of hyperammonemia, and increase in antioxidant capacity by decreasing MDA, ROS, and increasing CAT and GSH. In addition, the expressions of NF-κB, TNF-α, IL-1ß, caspase-3 and Bax was down-regulated while IL-10 and Bcl-2 expressions were up-regulated with taxifolin treatment. The recovery was confirmed by downregulation of iNOS and 8-OHdG expressions in our immunohistochemical analysis. Taxifolin treatment reduced the disrupting role of thioacetamide as seen by corrected hyperammonemia as well as preservation of astrocyte and hepatocyte structure. Elevated plus maze and locomotor activity tests also proved that taxifolin might repeal the neurobehavioral disabilities. In conclusion, taxifolin has shown hepatoprotective and neuroprotective roles with antioxidant and anti-inflammatory effects, as well as suppressing the excessive release of ammonia, and it eventually reversed neurobehavioral impairments.

Centella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis.

This study was designed to investigate the protective effects of Centella asiatica (CA) on cisplatin-induced hepatotoxicity and to clarify the underlying mechanism by biochemical, molecular, immunohistochemical, and histopathological analyses. Rats were pre-treated with two doses of CA (100 and 200 mg/kg, p.o.) for 14 consecutive days. Then, on the 15th day, hepatotoxicity was induced by a single cisplatin injection (10 mg/kg i.p.). On the 18th day, the rats were euthanized. CA effectively alleviated cisplatin-induced hepatic injury via reduction in AST, ALT, and ALP enzymes and a decrease in oxidative stress (decreased MDA and ROS, and increased SOD, CAT, and GSH). CA also mitigated the inflammatory damage by the inhibition of TNF-α, IL-1ß, and NF-κB. The liver expression of caspase-3 and Bax was downregulated, while Bcl-2 was upregulated. Moreover, immunohistochemical results confirmed the recovery with CA by downregulation of iNOS and 8-OHdG expression. These results showed that with its antioxidant, anti-inflammatory, and anti-apoptotic activities, CA could help alleviate the hepatotoxic effects of cisplatin chemotherapy.

Orally disintegrating tablet containing carbamazepine and levetiracetam: formulation and in vitro and in vivo characterization.

This study aimed to prepare and characterize the orally disintegrating tablet (ODT) formulations containing the combination of levetiracetam (LEV) and carbamazepine (CBZ) (CBZ + LEV combination) for the treatment of epilepsy. The ODT formulations were prepared using the lyophilization (L) and direct compression (DC) methods. The flowability of the mixed powders used for DC formulation was evaluated. The quality control tests for the ODTs were performed. Also, the antiepileptic effects of pure drugs, their combination, and the suspension of CBZ + LEV-DC-ODT formulation were evaluated in the rats with pentylenetetrazole (PTZ)-induced epilepsy model. The obtained results for the mixed powders of the DC formulation (angle of repose: 26.18 ± 0.794°; compressibility index: 15.24 ± 0.764%) suggest that the flow properties of the powder blend were suitable for the preparation of CBZ + LEV-ODT using DC method. The mean values of diameter and hardness of L-ODTs and DC-ODTs were found to be 16.87 mm and 16.18 mm and 11.96 N and 30.11 N, respectively. The friability of both formulations was <1%. Both formulations were disintegrated in seconds. Drugs in L-ODT had faster dissolution than those in DC-ODT. Compared to the seizure scores obtained for the groups treated with LEV or CBZ, generally, there was a higher decrease in seizure scores in the groups treated with CBZ + LEV combination or the suspension of CBZ + LEV-DC-ODTs. Consequently, the ODT formulations containing the CBZ + LEV combination might be beneficial in the treatment of epilepsy.

Effects of Achillea millefolium on cisplatin induced ocular toxicity: an experimental study.

Aim: Cisplatin is a widely used and highly effective anti-cancer agent and one of the limiting side effects of cisplatin is ocular toxicity. Achillea millefolium, also known as yarrow, is a plant that has been used for many years to treat various health problems including chemotherapy-related toxicities. Methods: The present investigation was designed to evaluate the biochemical, molecular and histopathological effects of Achillea Millefolium on cisplatin-induced oxidative and inflammatory ocular damage in rats. Twenty-four adult male rats were assigned randomly to four groups (n = 6) as (1) control, (2) cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Achillea millefolium (200 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Levels of total antioxidant capacity and total oxidant status, SOD, MDA, IL-1ß, and IL-10 were measured in ocular tissue. The mRNA expressions of TNF-α, nuclear factor kappa B and Caspase-3 were evaluated. Also, ocular sections were evaluated histopathologically.Results: Achillea Millefolium upregulated ocular antioxidant enzymes and downregulated inflammation. The SOD activity and total antioxidant capacity increased whereas total oxidant status and MDA levels decreased significantly at high dose group. High dose Achillea millefolium treatment reduced the IL-1ß concentrations, whereas IL-10 levels increased significantly in that group. Moreover, we observed that Achillea millefolium restored ocular histopathological structure and significantly suppressed apoptosis by reducing the expression of Caspase-3.Conclusion: Collectively, our results suggest that Achillea millefolium have protective effects against cisplatin-induced ocular toxicity and is a promising adjuvant therapy with the potential to prevent cisplatin related ocular toxicity.

Achillea millefolium alleviates testicular damage in paclitaxel-intoxicated rats via attenuation of testicular oxido-inflammatory stress and apoptotic responses.

The aim of this study was to investigate the effects of Achillea millefolium extract in paclitaxel-induced testicular toxicity in rats. The groups were designed as (1) control, (2) paclitaxel (8 mg/kg, intraperitoneally), (3) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (200 mg/kg, orally for 14 consecutive days) and (4) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Serum levels of testosterone, luteinising hormone and follicle-stimulating hormone, as well as total antioxidant capacity and total oxidant status were measured one day after receiving the last dose of Achillea millefolium extract. Testicular superoxide dismutase activity, malondialdehyde, tumour necrosis factor alpha and interleukin-1ß levels, the expressions of nuclear factor kappa B and caspase-3 were evaluated. In addition, testicular sections were evaluated histopathologically and 8-hydroxy-2'-deoxyguanosine was detected immunohistochemically. Achillea millefolium improved the levels of luteinising hormone, follicle-stimulating hormone and testosterone, upregulated testicular antioxidant enzymes and downregulated inflammation. Furthermore, we observed that Achillea millefolium restored testicular histopathological structure and significantly suppressed oxidative DNA damage and apoptosis by reducing the expression of caspase-3. Taken together, our results suggest that Achillea millefolium has protective effects against paclitaxel-induced testicular toxicity and is a promising natural product with the potential to improve male fertility.

Carbamazepine and levetiracetam-loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies.

Objective: The aim of this study was to develop the PLGA nanoparticles (NPs) containing carbamazepine (CBZ) and levetiracetam (LEV) combination (CBZ + LEV) for the treatment of epilepsy and to in vitro characterize the prepared NPs.Significance: LEV and CBZ, which are antiepileptic drugs, are used in the treatment of epilepsy. Nano-sized formulations are prepared to use for different purposes such as to improve the solubility/the physicochemical properties and bioavailability of drugs, to decrease their doses and frequency of administration, and to reduce side effects of drugs.Methods: CBZ + LEV-PLGA-NPs were prepared by a modified nanoprecipitation method and in vitro and in vivo characterized. Also, the antiepileptic effect of the NPs was evaluated in vivo in a rat epilepsy model.Results: The mean particle size and zeta potential of CBZ + LEV-PLGA-NPs were 180.62 ± 6.260 nm and -27.08 ± 3.110 mV, respectively. The values of encapsulation efficiency (EE%) of CBZ and LEV were 51.00 ± 5.944% and 2.05 ± 0.367%, respectively. CBZ showed a biphasic release profile with initial burst release followed by a sustained release. Ninety percent of CBZ was released from NPs within two days; however, % LEV release from NPs reached about 80% within 30 min.Conclusion: Our results showed that a decrease in seizure scores in the group treated with CBZ + LEV was observed and also, CBZ + LEV and CBZ + LEV-PLGA-NPs had similar antiepileptic activity. The NPs containing CBZ + LEV might be beneficial in the treatment of epilepsy.