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.

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.

The effects of Tendoflex® (polytendon complex) and Hypericum perforatum (St. John's wort oil) on repaired Achilles tendon healing in rats.

OBJECTIVES: This experimental study aims to examine the effects of Tendoflex® and Hypericum perforatum on tendon healing in rat models undergoing iatrogenic Achilles tendon rupture and similar surgical treatments. MATERIALS AND METHODS: Eighty Wistar albino rats weighing 250 to 350 g were randomly divided into four groups. Group A: Tendoflex® was administered orally as 1 capsule/2.5 kg daily by gavage. Group B: Hypericum perforatum was administered orally as 300 mg/kg daily by gavage. Group C: Tendoflex® and Hypericum perforatum were co-administered orally by gavage at the prespecified doses. Group D: No medication was given to the control group. Five rats from each group were sacrificed weekly, and the tissue samples were examined histologically, followed by the biomechanical tests of the Achilles tendon. RESULTS: In the mechanical testing, pulling forces were superior in all intervention groups and in all weeks over the control group. In particular, in the early periods (Weeks 1, 2, and 3), the mixed group showed the most favorable results, followed by the Hypericum perforatum group (p=0.010, p=0.591, and p=0.130, respectively). The most favorable collagen type I and type III expression values were found in the mixed and Hypericum perforatum groups at Weeks 2 and 3, respectively (p=0.025 and p=0.018). In the immunohistochemical and Western Blot examinations, extreme collagen type I and type III expression were detected in the mixed and Hypericum perforatum groups at Weeks 2, 3, and 4. CONCLUSION: Tensile strength of the Achilles tendon increased by using Hypericum perforatum and Tendoflex® following rupture and repair of the Achilles tendon in rats. The combined use of these two agents yielded the most favorable mechanical and histological results, particularly in the early period. This result may be related to the higher level of collagen type I and type III immunity in all groups, compared to the control group.

Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson's disease.

BACKGROUND: This study was designed to investigate the neuroprotective effects of bromelain, which is known to have anti-oxidant and anti-inflammatory properties, against the neurotoxicity (induced by 6-OHDA) in SH-SY5Y cells. METHODS AND RESULTS: To establish Parkinson's Disease (PD) model in cell culture conditions, SH-SY5Y cells were exposed to 200 µM 6-OHDA for 1 day. Prior to 6-OHDA treatment, SH-SY5Y cells had been pre-treated with bromelain (25 µg/mL, 50 µg/mL, 75 µg/mL and 100 µg/mL). After 1 day, cell viability was determined with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assays. Oxidative stress was assessed with total antioxidant capacity (TAC), total oxidant status (TOS), glutathione reductase (GR) and malondialdehyde (MDA) analyses. The effect of the bromelain in SH-SY5Ycells was also examined by 4',6-diamidino-2-phenylindole (DAPI) staining. We found that 6-OHDA increased LDH leakage, and cellular apoptosis in SH-SY5Y cells. 6-OHDA aggravated oxidative stress by increasing TOS, MDA and GR and eventually promoted apoptosis in SH-SY5Y cells, while pretreatment with bromelain attenuated these toxic effects of 6-OHDA. CONCLUSIONS: These findings indicated that bromelain, with its neuroprotective features can be useful for neuroprotection in PD.

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.