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Reevaluating ReveL Osteotomy: Gait, Function and Long-Term Outcomes in
Hallux Valgus Correction by Muhammad Khubaib Iftikhar in Orthopedic Research
Online Journal: Peer Reviewed Orthopedic Research
Online Journal
We read with great interest the study by Cissé et al. [1] which presents the outcomes of simultaneous bilateral isolated hallux valgus correction using the ReveL distal metatarsal osteotomy. The authors provide valuable insights into clinical, radiological, and pedobarographic results over a minimum two-year follow-up. However, we believe certain methodological aspects and clinical considerations warrant further discussion.
Firstly, while the study evaluates radiological correction parameters, a more comprehensive analysis of functional outcomes would have strengthened its conclusions. Hallux valgus correction is not solely about angular correction but also about long-term pain relief, joint mobility, and patient satisfaction. Validated scoring systems such as the Manchester-Oxford Foot Questionnaire (MOXFQ) or the Foot and Ankle Outcome Score (FAOS) would have added depth to the assessment of patient-reported outcomes [2].
Secondly, the pedobarographic evaluation, though useful, could benefit from comparison with preoperative gait assessments to better delineate biomechanical changes. Previous studies have highlighted that even after radiographic correction, alterations in forefoot loading patterns can persist, potentially predisposing patients to transfer metatarsalgia [3]. A longitudinal pedobarographic follow-up could provide further insights into functional restoration beyond structural realignment.
Furthermore, the study lacks a direct comparative analysis with other established osteotomy techniques, such as the Chevron or Scarf osteotomies. The assertion that the ReveL osteotomy offers superior outcomes would be more robust if supported by randomized controlled comparisons rather than single-cohort observations. Literature suggests that while minimally invasive techniques may reduce soft tissue trauma, concerns regarding stability and recurrence remain [4].
Additionally, there is limited discussion on postoperative rehabilitation protocols and their impact on long-term functional outcomes. Studies indicate that structured rehabilitation programs significantly influence recovery speed and recurrence rates following hallux valgus surgery [5]. Standardizing post-surgical rehabilitation strategies could enhance the overall success of the procedure.
Finally, the study does not address potential long-term
complications such as joint stiffness, recurrence rates, or adjacent
joint overload. Given that hallux valgus surgery aims to restore
long-term function, future investigations with extended follow-up
and stratification based on patient-specific factors (e.g., age, activity
level) would be beneficial [6].
In summary, while this study contributes to the growing body
of literature on hallux valgus correction, a more holistic evaluation
encompassing functional outcomes, biomechanical assessments,
comparative trials, and standardized rehabilitation protocols is
necessary for a conclusive appraisal of the ReveL osteotomy’s
efficacy.
The Efficacy of Sap Obtained from Commiphora gileadensis Against
Cadmium-Induced Liver Toxicity in Rats by Amal S Soliman in Research in Medical
& Engineering Sciences: Peer Reviewed Research in Medical
& Engineering Sciences
Cadmium (Cd), a toxic heavy metal, ranks among the top ten environmental threats to human health, adversely affecting vital organs such as the kidneys, liver, pancreas, lungs, and testes. This study investigates the protective effects of Commiphora gileadensis (CG) sap against Cd-induced liver damage in male rats. Forty-two healthy adult male albino rats were randomly divided into seven groups: G1 (control), G2 (50mg/L cadmium chloride in drinking water), G3 and G4 (100mg/kg and 400mg/kg CG sap, respectively), G5 (50mg/L cadmium chloride + 100mg/kg CG sap), G6 (50mg/L cadmium chloride + 400mg/kg CG sap), and G7 (1% Tween 80, 1mL/rat as a vehicle). Cadmium exposure significantly reduced the antioxidant capacity and impaired liver functions. However, co-administration of CG sap markedly ameliorated these adverse effects, improving antioxidant capacity and restoring hepatic function. These findings suggest that CG sap has potential as a natural therapeutic agent to mitigate cadmium toxicity and its associated environmental hazards.
The livers are critical organs responsible for xenobiotic metabolism and storage, making them highly susceptible to damage from toxic substances. Cadmium (Cd), a non-essential transition metal, is a significant environmental contaminant known for its toxicity to humans and animals. Cd exposure occurs through industrial and agricultural activities, as well as contaminated food, water, and cigarette smoke [1,2]. Due to its long biological half-life (25-30 years), Cd bioaccumulates in tissues, primarily in the liver, causing severe oxidative stress and tissue damage [3].
Cd toxicity is associated with various health complications, including hepatic syndrome, characterized by impaired liver functions and increased morbidity and mortality. The toxic effects of Cd are largely mediated by its induction of reactive oxygen species (ROS), leading to oxidative stress, mitochondrial dysfunction, and damage to cellular components [4,5]. Antioxidants, both synthetic and natural, have been investigated for their ability to counteract Cd-induced oxidative damage. Among natural antioxidants, plant-derived compounds such as phenolics and flavonoids have shown significant protective effects [6].
Commiphora gileadensis (CG), commonly known as Balessan,
is a medicinal plant native to arid regions, including Saudi Arabia.
Traditionally, CG sap has been used for its anti-inflammatory,
antimicrobial, and wound-healing properties [7,8]. Recent studies
have highlighted the antioxidant potential of CG sap, which may offer
protective effects against heavy metal toxicity [9,10]. This study
evaluates the ameliorative effects of CG sap on Cd-induced liver
damage in albino rats, with a focus on histopathological changes
and biochemical markers.
Commiphora gileadensis sap was collected by damaging the
bark of the plant in the Medina region of Saudi Arabia.
In Vitro antioxidant activity assessment
One g of plant sap was extracted with 10 mL of ethanol using a
magnetic stirrer at 1,000rpm (IKA, Staufen, Germany).
Total Phenolic Content (TPC)
TPC was estimated using the Folin-Ciocalteu method [11] with
gallic acid as the standard.
Cupric Reducing Antioxidant Capacity (CUPRAC)
The CUPRAC assay was performed as reported by [12], using
Trolox as the standard antioxidant. The experiment was conducted
in triplicates, with values expressed as Trolox equivalents per gram
of dry weight.
Total Flavonoid Content (TFC)
TFC was determined using the aluminum chloride colorimetric
method [13]. Absorbance was measured at 405nm, with results
expressed as quercetin equivalents (QE).
Ferric Reducing/Antioxidant Power (FRAP)
The FRAP assay was conducted following the method of [14],
using Trolox as the standard.
DPPH radical-scavenging activity
The DPPH assay was carried out using the method of [15],
with results measured at 517nm.
ABTS radical-scavenging activity
The ABTS assay was performed as described by [16], with
results expressed at 734nm.
Median Lethal Dose (LD50)
The LD50 of CG sap was determined using 12 male Swiss albino
mice (20-25g). The mice were divided into four groups (n=3 per
group) and acclimated for seven days. Doses of 1.0, 2.5, and 5.0g/
kg body weight of CG sap in 1% Tween 80 were administered orally.
Observations for mortality and behavioral changes were conducted
for 48 hours [17].
Animal Experimentation
Forty-two adult male albino rats (200-220g) were obtained
from the Faculty of Pharmacy, King Saud University, Riyadh,
Saudi Arabia. After a two-week acclimation period, the rats were
randomly divided into seven groups (n=6 per group) as follows:
Control Group (G1; NC): Normal drinking water and standard diet.
Positive Control (G2: Cd): 50mg/L cadmium chloride in drinking
water. Experimental Groups (G3: CG1, G4: CG4): 100mg/kg and
400mg/kg CG sap orally. Combination Groups (G5, G6): 50mg/L
cadmium chloride + 100mg/kg or 400mg/kg CG sap orally. Vehicle
Control (G7): 1mL of 1% Tween 80 orally.
All treatments were administered daily for 60 days. Cadmium
chloride was supplied via drinking water, while CG sap and vehicle
were administered orally by gavage [18].
Blood sampling and histopathological examination
At the end of the experimental period, blood samples were
collected under light ether anesthesia for serum preparation to
measure biochemical parameters using commercial kits. Liver
tissues were harvested, preserved in 10% buffered formalin, and
processed for histopathological analysis.
Statistical analysis
Results were reported as mean ± SEM (Standard Error of
Mean). To assess the influence of the seven treatment groups on
the different biochemical parameters, one- way analysis of variance
(ANOVA) by Tukey multiple tests as post hoc test were used. The
value of P<0.05 was used to indicate statistical significance. ALL
Analyses were done using Statistical Package (IBM SPSS Statistics,
version 26).
The median lethal dose (LD50) of C. gileadensis sap
The findings indicated that none of the tested doses of
Commiphora gileadensis, even at levels as high as 5000mg per
kilogram of body weight, resulted in no fatalities within the various
groups (Table 1).
Table 1:The number of Mortality of different groups of mice with different administered doses.
In vitro assessment of antioxidant activity
C. gileadensis had strong scavenging values depend on our
result (Figure 1). The results showed that DPPH value of CG to be
75.27%, the ABTS value of CG was 98%, the TPC value of CG to be
101.47mg GAE/g and the TFC value of CG to be 77.13mg QE/g and
the values of FRAP and CUPRAC were 40.72 and 36.93 respectively.
Effect of CG sap, and cadmium chloride on serum
antioxidant concentration
Table 2:Effect of CG sap, and cadmium chloride
on antioxidant concentration of CAT, MDA and total
antioxidant.
NC (normal control): Cd (cadmium): CG1 (Commiphora
gileadensis 100mg/kg b. wt.): CG4 (Commiphora
gileadensis 400mg/kg b. wt.): Values within the same
column carrying different letters are significantly different
at P<0.05 based on Tukey post hoc multiple comparison
test. Values are expressed as mean ± S.E. (N=6 rats).
Data observed that administration of C. gileadensis sap non
significantly affected the serum level of catalase, total antioxidants
and malondialdehyde (MDA) compared with the values of control
groups (Table 2). The present data showed a significant (P<0.05)
decreased in the serum level of catalase enzyme and total
antioxidants in cadmium chloride treated group compared to all
other groups of the study. While co- administration of C. gileadensis
sap plus cadmium chloride significantly enhanced the values of
serum levels of catalase enzyme; and total antioxidants and these
values did not differ significantly with those of control groups.
Administration of cadmium chloride significantly increased the
serum level of MDA compared to other groups of the experiment.
However, co-administration of C. gileadensis sap significantly
decreased the MDA level but remained higher significantly than
control values (Table 2).
Biochemical analysis
Biochemical analysis of various damage and function
markers were analyzed. These markers include liver damage and
function markers such as alanine transaminase (ALT), aspartate
transaminase (AST), alkaline phosphatase (ALP), total protein (TP)
and albumin (ALB). These tests aids determination of which part of
the liver is damaged, and depending on the pattern of elevation, can
assist organizing a differential diagnosis. Besides these markers,
the kidney function markers such as the urea, creatinine and uric
acid levels in the blood serum were investigated.
The liver function markers were analyzed including ALT, AST
and ALP as shown in Table 3. As can be observed from Table, A
significant increase in AST (305.11±15.03), ALP (261.16±8.35), and
ALT (144.83±7.79) levels in the blood serum is clear in CD cohort
which indicates the induction of liver injury. This reduction was alsoobserved
even when the C. gileadensis dose to 100 and 400mg. The
effect and reduction of liver function marker upon exposure to
CD- C. gileadensis contributes to the potential protective effect of C.
gileadensis against liver injury.
Table 3:The effect of different treatments on the serum
levels of ALP, ALT and AST of rats intoxicated with CD for
8 weeks (values are expressed as mean ± SE.
NC (normal control): Cd (cadmium): CG1 (Commiphora
gileadensis 100mg/kg b. wt.): CG4 (Commiphora
gileadensis 400mg/kg b. wt.): Values within the same
column carrying different letters are significantly different
at P<0.05 based on Tukey post hoc multiple comparison
test. Values are expressed as mean ± S.E. (N=6 rats).
Histopathological examination of liver in the different
groups
Control group: No histopathological changes were detected
in the examined livers of these rats. Figure 2A revealed normal
histological criteria.
Cadmium chloride group: The livers of the treated rats showed
congestion and dilatation of central and portal veins (Figure 2B).
focal aggregates of lymphocytes and macrophages, surrounded
by coagulative necrosis of hepatocytes characterized by loss of
cellular detail, individualized shrunken hepatocytes with hyper
eosinophilic cytoplasm and pyknotic nuclei (Figure 2C).
Figure 2:A. Liver of control rat showing normal histological appearance of central vein (CV) and hepatocytes (H).
H&E stainx200.
B. Liver of rat administered 50mg cadmium chloride showing congestion and dilatation of portal vein (PV). H&E
stainx200.
C. Liver of rat administered 50mg cadmium chloride showing focal aggregates (asterisk) of lymphocytes
and macrophages, surrounded by coagulative necrosis of hepatocytes characterized by loss of cellular detail,
individualized shrunken hepatocytes with hyper eosinophilic cytoplasm and pyknotic nuclei (arrow). H&E stainx200.
C. gileadensis sap 100mg/ kg b. wt. group: The liver showed
normal histological appearance like control group. Occasionally, the
liver showed mild congestion of central veins (Figure 3A).
C. gileadensis sap 400mg/ kg b. wt. group: The liver showed
normal histological appearance like control group. Occasionally,
the liver showed congestion of portal veins and mild lymphocytic
infiltrate in portal areas (Figure 3B).
C. gileadensis sap 400mg/ kg b. wt. plus cadmium chloride
group: The livers showed mild congestion of central veins with
normal histological appearance of hepatocytes and portal areas
(Figure 3C).
Figure 3:A. Liver of rat administered 100mg plant sap/kg b. wt. showing mild congestion of central veins (CV)
and normal histological appearance of hepatocytes. H&E stain x 200.
B. Liver of rat administered 400mg plant sap/kg b. wt. showing congestion of portal vein (PV) and mild
lymphocytic (arrow) infiltrate in portal areas. H&E stain x 200.
C. Liver of rat administered 400mg plant sap/kg b. wt. and 50mg cadmium chloride showing mild congestion
of central veins (CV) with normal histological appearance of hepatocytes (H) and portal areas (PA). H&E stain x 200.
D. Liver of rat administered 400mg plant sap/kg b. wt. and 50mg cadmium chloride showing mild biliary
hyperplasia and small numbers of lymphocytes (arrowhead) and macrophages in portal areas. H&E stain x 400.
This study is the first to explore the protective effects
of Commiphora gileadensis (CG) sap against cadmium (Cd)-
induced toxicity in liver tissues. Plants have large number of
bioactive compounds with high antioxidant activity. Studies for
the determination of the antioxidant activity of different plant
species could contribute to revealing the value of these species
as a source of new antioxidant compounds. Plants live in habitats
with extreme environmental conditions (high temperatures, water
stress, and high light irradiation in summer), for which they have
developed different adaptive mechanisms, both morphological
and physiological. One of these mechanisms is the prevention of
oxidative stress, keeping ROS under dangerous levels [19], and
using them for efficient signaling [20]. Secondary metabolites
of plants, specifically phenols, can adjust the concentration of
ROS, thus activating a network of biochemical events to increase
tolerance, hence the importance of studying the antioxidant activity
of typical plant species as C. gileadensis. The protective effects
against oxidative stress are attributed to the natural antioxidants
found in herbs and spices. These aromatic ingredients harbor
compounds such as polyphenols, flavonoids, and phenolic
compounds, which act as scavengers of free radicals, however
antioxidants are substances that can scavenge free radicals and
prevent the oxidative damage they generate in cells. In the present
study, C. gileadensis sap had strong antioxidant activity by studying
its DPPH, ABTS, FRAP and CUPRAC values. Some authors, confirmed
the previous findings on some parts of CG other than its sap
as leaves and bark. [21], reported the DPPH value of CG to be
75.27% which is lower than the value reported in this research.
However, [22] reported higher values than in the present study.
While, the ABTS value of CG to be 98% which is higher than the
value reported in this research. [21] reported the TPC value of CG
to be 101.47 mg GAE/g and the value was lower than the value
reported in this research. [23] reported the TFC value of CG to
be 77.13mg QE/g which is lower than the value reported in this
research. However, there is no report in the literature of the values
of FRAP and CUPRAC. The differences between results may be due
to different parts used, extraction conditions such as methodology
and solvents used in the extraction. The differences in results also,
may be due to geographical locations of samples.
C. gileadensis sap is of wide safety margin as confirmed in the
present study as LD50 was above 5g /kg b. wt. These results align
with previous research conducted by [24] who reported that C.
gileadensis sap safe up to 5g/kg b. wt. Consequently, any substance
that demonstrates no harmful effects at a dosage of 5000mg/
kg is categorized as being ‘practically non-toxic.’ Based on these
outcomes, it can be concluded that Commiphora gileadensis sap is
regarded as safe and practically non- toxic [25]. Cadmium is one of
the most toxic heavy metals and affects both animals and humans
via induction of cellular oxidative stress and subsequent elevation
of free radicals. Strong evidence suggests the harmful effect of
cadmium. The livers are the organs with the highest concentration
of cadmium present, after absorption [26]. When cadmium enters
the body, it is transported into the bloodstream via erythrocytes
and albumin and is then accumulated in liver and gut [27]. Cadmium
excretion from the body is slow and occurs via the kidneys, urine,
saliva, and milk during lactation. Cd exposure can result in a
variety of adverse effects, such as renal and hepatic dysfunction,
pulmonary edema, testicular damage, osteo-malacia, and damage to
the adrenals and hemopoietic system [28]. It has been proved that
after exposure, Cd enters the blood and binds to the erythrocyte
membranes and blood albumin and then is transported to liver,
where it bounds to metallothionein (MT) [28]. The Cd-MT complex
is then released back into circulation [29]. and accumulates in the
blood system, kidney, liver, lung, testis, brain, and bone [30].
In the current study, liver injury was evident in the Cd group,
manifested by decreased total protein levels, increased liver
enzymes, AST, ALT and ALP. These results are in agreement with
earlier studies [31,32]. Recent reports have suggested that lysosome
instability caused by Cd toxicity resulted in the leakage of hepatic
enzymes, including ALT, ALP and AST, into the bloodstream [32]. CG
sap is rich source of polyphenols. Polyphenols have been reported
to possess a membrane stabilizing activity by inhibiting the
generation of ROS induced by Cd and maintain the cell membrane
structural integrity [33]. Our findings exhibited elevation in liver
enzymes in Cd-treated group. These findings come in the same
line with [34], who revealed that; Cd toxicity causing hepatic cell
damage and its enzymes AST, ALP and ALT released into circulation,
therefore the level of these enzymes in blood elevated than normal.
Histological examination of liver tissue showed liver injury in the
Cd-treated group, where hepatocytes lost their characteristic
regular arrangement. Most hepatocytes exhibited vacuolation, and
their nuclei were partially pyknotic. In contrast, CG a co- treatment
showed hepatic-protective effects, proven by restoration of liver
structure and function in these groups. The hepatic-protective
effects of CG sap observed in this study, supporting the opinion
that CG restored liver architecture and function following cadmium
toxicity.
These histological abnormalities were found to be reduced in
CG + Cd groups. The co- treatments with CG led to almost complete
restoration of the Cd induced renal damage and restored the
standard values of the kidney function markers.
Cd-induced hepatic dysfunction in this study was most likely
due to an imbalance of oxidant/antioxidant capacity in the tissues.
The present study showed a significant increase in MDA levels and a
decrease in the activity of antioxidant enzymes, such as serum total
antioxidants and CAT. The endogenous antioxidants are important
scavengers of free radicals, which eventually lead to cellular
dysfunction and death [6]. Our findings agreed with previous
reports demonstrating that cadmium induces kidney toxicity by
enhancing ROS formation and GSH consumption and inhibiting
an antioxidant-mediated defense system [33]. Additionally, the
nephroprotective effect of CG was owned to the improvement of
renal oxidation and decrease of serum creatinine urea levels which
are in consistence with [35]. In the present study, CG sap contains
a high content of flavonoids. [36] studied one of the main actions
of flavonoids, which enhanced renal function and diminished
apoptotic and oxidative stress markers. Thus, the properties of
CG may cause some of the Cd to be retained, preventing further
adverse effects usually induced by toxic metals. In the current study,
the observed Cd- induced hepatic histopathological abnormalities
are consistent with previous results depicting similar alterations in
rats treated with Cd administered as CdCl2. Most importantly, our
study has shown that CG pretreatment possesses potent hepatic
protective and antioxidative properties against cadmium toxicity.
Collectively, administration of cadmium chloride induces
adverse effects on the liver functions and decreases the
antioxidative status. Co-administration of CG sap with cadmium
significantly mitigated the previous hazard effects by ameliorating
the antioxidant status. The plant sap showed no signs of toxicity
were observed during the acute toxicity study and the LD50 value
indicates that sap is to be safe. Phytochemical investigation is also
proposed to isolate the active fraction and eventually the pure
compound.
The Researchers would like to thank the Deanship of Graduate
Studies and Scientific Research at Qassim University for financial
support (QU-APC-2024-9/1).
AL-Howiriny T, AL-Sohaibani M, AL-said M, AL-Yahya M, EL-Tahir K, et al. (2004) Hepatoprotective properties of Commiphora opobalsamum ("Balessan"), a traditional medicinal plant of Saudi Arabia. Drugs under Experimental and Clinical Research 30: 213-20.
AL-Mahbashi HM, EL-Shaibany A, Saad FA (2015) Evaluation of acute toxicity and antimicrobial effects of the bark extract of Bisham (Commiphora gileadensis ). Journal of Chemical and Pharmaceutical Research 7: 810-814.
Ecobichon DJ (1997) The basis of toxicity testing, CRC press p. 211.
